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New cancer treatment may reawaken the immune system

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Immunotherapy is a promising strategy to treat cancer by stimulating the body’s own immune system to destroy tumor cells, but it only works for a handful of cancers. MIT researchers have now discovered a new way to jump-start the immune system to attack tumors, which they hope could allow immunotherapy to be used against more types of cancer.

Their novel approach involves removing tumor cells from the body, treating them with chemotherapy drugs, and then placing them back in the tumor. When delivered along with drugs that activate T cells, these injured cancer cells appear to act as a distress signal that spurs the T cells into action.

“When you create cells that have DNA damage but are not killed, under certain conditions those live, injured cells can send a signal that awakens the immune system,” says Michael Yaffe, who is a David H. Koch Professor of Science, the director of the MIT Center for Precision Cancer Medicine, and a member of MIT’s Koch Institute for Integrative Cancer Research.

In mouse studies, the researchers found that this treatment could completely eliminate tumors in nearly half of the mice.

Yaffe and Darrell Irvine, who is the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and Materials Science and Engineering, and an associate director of the Koch Institute, are the senior authors of the study, which appears today in Science Signaling . MIT postdoc Ganapathy Sriram and Lauren Milling PhD ’21 are the lead authors of the paper.

T cell activation

One class of drugs currently used for cancer immunotherapy is checkpoint blockade inhibitors, which take the brakes off of T cells that have become “exhausted” and unable to attack tumors. These drugs have shown success in treating a few types of cancer but do not work against many others.

Yaffe and his colleagues set out to try to improve the performance of these drugs by combining them with cytotoxic chemotherapy drugs, in hopes that the chemotherapy could help stimulate the immune system to kill tumor cells. This approach is based on a phenomenon known as immunogenic cell death, in which dead or dying tumor cells send signals that attract the immune system’s attention.

Several clinical trials combining chemotherapy and immunotherapy drugs are underway, but little is known so far about the best way to combine these two types of treatment.

The MIT team began by treating cancer cells with several different chemotherapy drugs, at different doses. Twenty-four hours after the treatment, the researchers added dendritic cells to each dish, followed 24 hours later by T cells. Then, they measured how well the T cells were able to kill the cancer cells. To their surprise, they found that most of the chemotherapy drugs didn’t help very much. And those that did help appeared to work best at low doses that didn’t kill many cells.

The researchers later realized why this was so: It wasn’t dead tumor cells that were stimulating the immune system; instead, the critical factor was cells that were injured by chemotherapy but still alive.

“This describes a new concept of immunogenic cell injury rather than immunogenic cell death for cancer treatment,” Yaffe says. “We showed that if you treated tumor cells in a dish, when you injected them back directly into the tumor and gave checkpoint blockade inhibitors, the live, injured cells were the ones that reawaken the immune system.”

The drugs that appear to work best with this approach are drugs that cause DNA damage. The researchers found that when DNA damage occurs in tumor cells, it activates cellular pathways that respond to stress. These pathways send out distress signals that provoke T cells to leap into action and destroy not only those injured cells but any tumor cells nearby.

“Our findings fit perfectly with the concept that ‘danger signals’ within cells can talk to the immune system, a theory pioneered by Polly Matzinger at NIH in the 1990s, though still not universally accepted,” Yaffe says.  

Tumor elimination

In studies of mice with melanoma and breast tumors, the researchers showed that this treatment eliminated tumors completely in 40 percent of the mice. Furthermore, when the researchers injected cancer cells into these same mice several months later, their T cells recognized them and destroyed them before they could form new tumors.

The researchers also tried injecting DNA-damaging drugs directly into the tumors, instead of treating cells outside the body, but they found this was not effective because the chemotherapy drugs also harmed T cells and other immune cells near the tumor. Also, injecting the injured cells without checkpoint blockade inhibitors had little effect.

“You have to present something that can act as an immunostimulant, but then you also have to release the preexisting block on the immune cells,” Yaffe says.

Yaffe hopes to test this approach in patients whose tumors have not responded to immunotherapy, but more study is needed first to determine which drugs, and at which doses, would be most beneficial for different types of tumors. The researchers are also further investigating the details of exactly how the injured tumor cells stimulate such a strong T cell response.

The research was funded, in part, by the National Institutes of Health, the Mazumdar-Shaw International Oncology Fellowship, the MIT Center for Precision Cancer Medicine, and the Charles and Marjorie Holloway Foundation.

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‘Dramatic’ inroads against aggressive brain cancer

Cutting-edge therapy shrinks tumors in early glioblastoma trial

Haley Bridger

Mass General Communications

A collaborative project to bring the promise of cell therapy to patients with a deadly form of brain cancer has shown dramatic results among the first patients to receive the novel treatment.

In a paper published Wednesday in The New England Journal of Medicine, researchers from Mass General Cancer Center shared the results for the first three patient cases from a Phase 1 clinical trial evaluating a new approach to CAR-T  therapy for glioblastoma.

Just days after a single treatment, patients experienced dramatic reductions in their tumors, with one patient achieving near-complete tumor regression. In time, the researchers observed tumor progression in these patients, but given the strategy’s promising preliminary results, the team will pursue strategies to extend the durability of response.

Left: MRI in Participant 3 before infusion. Right: After infusion on day five.

Image courtesy of The New England Journal of Medicine

“This is a story of bench-to-bedside therapy, with a novel cell therapy designed in the laboratories of Massachusetts General Hospital and translated for patient use within five years, to meet an urgent need,” said co-author Bryan Choi , a neurosurgeon at Harvard-affiliated Mass General and an assistant professor at Harvard Medical School. “The CAR-T platform has revolutionized how we think about treating patients with cancer, but solid tumors like glioblastoma have remained challenging to treat because not all cancer cells are exactly alike and cells within the tumor vary. Our approach combines two forms of therapy, allowing us to treat glioblastoma in a broader, potentially more effective way.”

The new approach is a result of years of collaboration and innovation springing from the lab of Marcela Maus , director of the Cellular Immunotherapy Program and an associate professor at the Medical School. Maus’ lab has set up a team of collaborating scientists and expert personnel to rapidly bring next-generation genetically modified T cells from the bench to clinical trials in patients with cancer.

“We’ve made an investment in developing the team to enable translation of our innovations in immunotherapy from our lab to the clinic, to transform care for patients with cancer,” said Maus. “These results are exciting, but they are also just the beginning — they tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease. We haven’t cured patients yet, but that is our audacious goal.”

CAR-T (chimeric antigen receptor T-cell) therapy works by using a patient’s own cells to fight cancer — it is known as the most personalized way to treat the disease. A patient’s cells are extracted, modified to produce proteins on their surface called chimeric antigen receptors, and then injected back into the body to target the tumor directly. Cells used in this study were manufactured by the Connell and O’Reilly Families Cell Manipulation Core Facility of the Dana-Farber/Harvard Cancer Center.

CAR-T therapies have been approved for the treatment of blood cancers, but the therapy’s use for solid tumors is limited. Solid tumors contain mixed populations of cells, allowing some malignant cells to continue to evade the immune system’s detection even after treatment with CAR-T. Maus’ team is working to overcome this challenge by combining two previously separate strategies: CAR-T and bispecific antibodies, known as T-cell engaging antibody molecules. The version of CAR-TEAM for glioblastoma is designed to be directly injected into a patient’s brain.

In the new study, the three patients’ T cells were collected and transformed into the new version of CAR-TEAM cells, which were then infused back into each patient. Patients were monitored for toxicity throughout the duration of the study. All patients had been treated with standard-of-care radiation and temozolomide chemotherapy and were enrolled in the trial after disease recurrence.

• A 74-year-old man had his tumor regress rapidly but transiently after a single infusion of the new CAR-TEAM cells.
• A 72-year-old man was treated with a single infusion of CAR-TEAM cells. Two days after receiving the cells, an MRI showed a decrease in the tumor’s size by 18 percent. By day 69, the tumor had decreased by 60 percent, and the response was sustained for more than six months.
• A 57-year-old woman was treated with CAR-TEAM cells. An MRI five days after the infusion showed near-complete tumor regression.

The authors note that despite the remarkable responses among the first three patients, they observed eventual tumor progression in all the cases, though in one case, there was no progression for over six months. Progression corresponded in part with the limited persistence of the CAR-TEAM cells over the weeks following infusion. As a next step, the team is considering serial infusions or preconditioning with chemotherapy to prolong the response.

“We report a dramatic and rapid response in these three patients. Our work to date shows signs that we are making progress, but there is more to do,” said co-author Elizabeth Gerstner, a Mass General neuro-oncologist.

In addition to Choi, Maus, and Gerstner, other authors are Matthew J. Frigault, Mark B. Leick. Christopher W. Mount, Leonora Balaj, Sarah Nikiforow, Bob S. Carter, William T. Curry, and Kathleen Gallagher.

The study was supported in part by the National Gene Vector Biorepository at Indiana University, which is funded under a National Cancer Institute contract.

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Scientists create tailored drug for aggressive breast cancer

Scientists have used breast cancer cells' weakness against themselves by linking a tumour-selective antibody with a cell-killing drug to destroy hard-to-treat tumours.

The research, published today in Clinical Cancer Research by a team from King's College London and funded by Breast Cancer Now, marks a new method in cancer treatment.

The discovery is particular to triple negative breast cancer, which makes up 15% of all diagnosed breast cancer. This type of breast cancer is typically aggressive, resistant to chemotherapy, has a lower survival rate and is more common in women under 40.

Usual treatment involves surgery, chemotherapy and radiotherapy, however this type of cancer can evade the drugs and return to spread again.

The scientists conducted data analysis using over 6000 breast cancer samples to investigate the properties of breast cancer cells that are associated with aggressive and chemotherapy-resistant cancers.

They studied the cancer's biology, what is expressed in the tumour and the cell surface, and the cell's insides to understand how the cancer cells escape from cancer drugs. They established the presence of the cancer cell surface marker EGFR along with oncogenic molecules cyclin-dependent kinases (CDK), which are responsible for cell division and proliferation.

They used this knowledge against the cancer cells to link cetuximab, a tumour-selective antibody that targets the EGFR protein expressed in this type of cancer, with a CDK-blocking drug to create a tailored drug for breast cancer. Because the antibody drug conjugate specifically targets the cancer cell, it may be possible to administer a lower inhibitor dose than usual which means it's less toxic for the patient.

Lead author Professor Sophia Karagiannis, from King's College London, said: "We were on the hunt for cancer's vulnerabilities and now we've found out how we can guide our therapies to one of these. We combined these two drugs to create a tailored antibody drug conjugate for patients with this aggressive cancer. The antibody guides the toxic drug directly to the cancer cell which offers the possibility for a lower dose and less adverse side effects to be experienced.

"More work needs to be done before this therapy can reach the clinic, but we expect that this can offer new treatment options for cancers with unfavourable prognosis. Beyond this antibody drug conjugate, we hope that our concept will lead the way for new antibody drug conjugates of this type to be tailored to patient groups likely to benefit."

Lead research scientist Dr Anthony Cheung from King's College London said: ''Triple negative breast cancer represents a molecularly and clinically diverse disease. By exploiting EGFR overexpression and dysregulated cell cycle molecules in selected patient groups, the antibody drug conjugate, but not the antibody alone, could stop the cancer cell from dividing and engender cytotoxic functions specifically against the cancer cells.''

Dr Simon Vincent, director of services, support and influencing at Breast Cancer Now, which funded this research, said: "Each year, around 8,000 women in the UK are diagnosed with triple negative breast cancer, which is typically more aggressive than other breast cancers and more likely to return or spread following treatment.

"This exciting research has not only improved our understanding of the properties of aggressive breast cancer cells that are resistant to chemotherapy but has also brought us closer to developing a targeted therapy that destroys these cancer cells while minimising side effects for patients.

"While further research is needed before this treatment can be used in people, this is an exciting step forward in developing targeted therapies for triple negative breast cancer, and we look forward to seeing how these findings could lead to new and effective ways of tackling this devastating disease."

• Breast Cancer
• Lung Cancer
• Colon Cancer
• Brain Tumor
• Ovarian Cancer
• Monoclonal antibody therapy
• Chemotherapy
• Mammography
• Breast cancer
• Esophageal cancer

Story Source:

Materials provided by King's College London . Note: Content may be edited for style and length.

Journal Reference :

• Anthony Cheung, Alicia M. Chenoweth, Annelie Johansson, Roman Laddach, Naomi Guppy, Jennifer Trendell, Benjamina Esapa, Antranik Mavousian, Blanca Navarro-Llinas, Syed Haider, Pablo Romero-Clavijo, Ricarda M. Hoffmann, Paolo Andriollo, Khondaker Miraz Rahman, Paul Jackson, Sophia Tsoka, Sheeba Irshad, Ioannis Roxanis, Anita Grigoriadis, David E. Thurston, Christopher J. Lord, Andrew N.J. Tutt, Sophia N. Karagiannis. Anti-EGFR antibody-drug conjugate carrying an inhibitor targeting CDK restricts triple-negative breast cancer growth . Clinical Cancer Research , 2024; DOI: 10.1158/1078-0432.CCR-23-3110

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Medical advances are continuing to help the world fight cancer. Image:  Unsplash/National Cancer Institute

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This article was originally published in May 2022, and most recently updated in May 2024 .

• Cancer is one of the world’s biggest killers, with around 10 million deaths per year due to the disease.
• Scientists are using artificial intelligence, DNA sequencing, precision oncology and other technologies to improve treatment and diagnosis.
• The Centre for the Fourth Industrial Revolution India, a collaboration with the World Economic Forum, hopes to accelerate 18 cancer interventions.

Cancer kills around 10 million people a year and is a leading cause of death globally, according to the World Health Organization.

Breast, lung and colon cancer are among the most common. Death rates from cancer were falling before the pandemic . But COVID-19 caused a big backlog in diagnosis and treatment .

There is some good news, however. Medical advances are accelerating the battle against cancer. Here are 10 recent developments.

Test to identify 18 early-stage cancers

Researchers in the US have developed a test they say can identify 18 early-stage cancers. Instead of the usual invasive and costly methods, Novelna's test works by analyzing a patient's blood protein. In a screening of 440 people already diagnosed with cancer, the test correctly identified 93% of stage 1 cancers in men and 84% in women. The researchers believe the findings "pave the way for a cost-effective, highly accurate, multi-cancer screening test that can be implemented on a population-wide scale". It's early days, however. With such a small sample screening and a lack of information on co-existing conditions, the test is currently more of "a starting point for developing a new generation of screening tests for the early detection of cancer".

Seven-minute cancer treatment jab

England's National Health Service (NHS) is to be the first in the world to make use of a cancer treatment injection , which takes just seven minutes to administer, rather than the current time of up to an hour to have the same drug via intravenous infusion. This will not only speed up the treatment process for patients, but also free up time for medical professionals. The drug, Atezolizumab or Tecentriq, treats cancers including lung and breast, and it's expected most of the 3,600 NHS patients in England currently receiving it intravenously will now switch to the jab.

Precision oncology

Precision oncology is the “ best new weapon to defeat cancer ”, the chief executive of Genetron Health, Sizhen Wang, says in a blog for the World Economic Forum. This involves studying the genetic makeup and molecular characteristics of cancer tumours in individual patients. The precision oncology approach identifies changes in cells that might be causing the cancer to grow and spread. Personalized treatments can then be developed. The 100,000 Genomes Project, a National Health Service initiative, studied more than 13,000 tumour samples from UK cancer patients , successfully integrating genomic data to more accurately pin-point effective treatment. Because precision oncology treatments are targeted – as opposed to general treatments like chemotherapy – it can mean less harm to healthy cells and fewer side effects as a result.

Artificial intelligence fights cancer

In India, World Economic Forum partners are using emerging technologies like artificial intelligence (AI) and machine learning to transform cancer care. For example, AI-based risk profiling can help screen for common cancers like breast cancer, leading to early diagnosis. AI technology can also be used to analyze X-rays to identify cancers in places where imaging experts might not be available. These are two of 18 cancer interventions that The Centre for the Fourth Industrial Revolution India, a collaboration with the Forum , hopes to accelerate.

Greater prediction capabilities

Lung cancer kills more people in the US yearly than the next three deadliest cancers combined. It's notoriously hard to detect the early stages of the disease with X-rays and scans alone. However, MIT scientists have developed an AI learning model to predict a person's likelihood of developing lung cancer up to six years in advance via a low-dose CT scan. Trained using complex imaging data, 'Sybil' can forecast both short- and long-term lung cancer risk, according to a recent study. "We found that while we as humans couldn't quite see where the cancer was, the model could still have some predictive power as to which lung would eventually develop cancer," said co-author Jeremy Wohlwend.

Clues in the DNA of cancer

At Cambridge University Hospitals in England, the DNA of cancer tumours from 12,000 patients is revealing new clues about the causes of cancer, scientists say. By analyzing genomic data, oncologists are identifying different mutations that have contributed to each person’s cancer. For example, exposure to smoking or UV light, or internal malfunctions in cells. These are like “fingerprints in a crime scene”, the scientists say – and more of them are being found. “We uncovered 58 new mutational signatures and broadened our knowledge of cancer,” says study author Dr Andrea Degasperi, from Cambridge’s Department of Oncology.

Liquid and synthetic biopsies

Biopsies are the main way doctors diagnose cancer – but the process is invasive and involves removing a section of tissue from the body, sometimes surgically, so it can be examined in a laboratory. Liquid biopsies are an easier and less invasive solution where blood samples can be tested for signs of cancer. Synthetic biopsies are another innovation that can force cancer cells to reveal themselves during the earliest stages of the disease.

The application of “precision medicine” to save and improve lives relies on good-quality, easily-accessible data on everything from our DNA to lifestyle and environmental factors. The opposite to a one-size-fits-all healthcare system, it has vast, untapped potential to transform the treatment and prediction of rare diseases—and disease in general.

But there is no global governance framework for such data and no common data portal. This is a problem that contributes to the premature deaths of hundreds of millions of rare-disease patients worldwide.

The World Economic Forum’s Breaking Barriers to Health Data Governance initiative is focused on creating, testing and growing a framework to support effective and responsible access – across borders – to sensitive health data for the treatment and diagnosis of rare diseases.

The data will be shared via a “federated data system”: a decentralized approach that allows different institutions to access each other’s data without that data ever leaving the organization it originated from. This is done via an application programming interface and strikes a balance between simply pooling data (posing security concerns) and limiting access completely.

The project is a collaboration between entities in the UK (Genomics England), Australia (Australian Genomics Health Alliance), Canada (Genomics4RD), and the US (Intermountain Healthcare).

CAR-T-cell therapy

A treatment that makes immune cells hunt down and kill cancer cells was declared a success for leukaemia patients in 2022. Known as CAR-T-cell therapy, it involves removing and genetically altering immune cells, called T cells, from cancer patients. The altered cells then produce proteins called chimeric antigen receptors (CARs), which can recognize and destroy cancer cells. In the journal Nature , scientists at the University of Pennsylvania announced that two of the first people treated with CAR-T-cell therapy were still in remission 12 years on.

However, the US Food and Drug Administration is currently investigating whether the process can in fact cause cancer , after 33 cases of secondary cancer were observed in patients receiving CAR-T therapies. The jury is still out as to whether the therapy is to blame but, as a precaution, the drug packaging now carries a warning.

Fighting pancreatic cancer

Pancreatic cancer is one of the deadliest cancers. It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years. At the University of California San Diego School of Medicine, scientists developed a test that identified 95% of early pancreatic cancers in a study. The research, published in Nature Communications Medicine , explains how biomarkers in extracellular vesicles – particles that regulate communication between cells – were used to detect pancreatic, ovarian and bladder cancer at stages I and II.

Have you read?

Cancer: how to stop the next global health crisis, how to improve access to cancer medicines in low and middle-income countries, why is cancer becoming more common among millennials, a tablet to cut breast cancer risk.

A drug that could halve the chance of women developing breast cancer is being tested out by England's National Health Service (NHS). It will be made available to almost 300,000 women seen as being at most risk of developing breast cancer, which is the most common type of cancer in the UK . The drug, named anastrozole, cuts the level of oestrogen women produce by blocking the enzyme aromatase . It has already been used for many years as a breast cancer treatment but has now been repurposed as a preventive medicine. “This is the first drug to be repurposed through a world-leading new programme to help us realize the full potential of existing medicines in new uses to save and improve more lives on the NHS," says NHS Chief Executive Amanda Pritchard.

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World Economic Forum articles may be republished in accordance with the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License, and in accordance with our Terms of Use.

The views expressed in this article are those of the author alone and not the World Economic Forum.

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Researchers in the Cochran lab, including Jack Silberstein (center), led the effort to capture an atomic-scale snapshot of the protein LAG-3. This protein has recently gained popularity for use in certain cancer treatments but knowledge of its structure and function has been incomplete, until now. (Image credit: Christophe Wu)

Some cancerous tumors hijack proteins that act as “brakes” on our immune system and use them to form a sort of shield against immune recognition. Immunotherapy treatments have been created that turn off these “brakes” and allow our body to attack foreign-looking cancer cells. To further advance such treatments, researchers at Stanford University and New York University have published a new structure of one of these brake proteins, LAG-3. Their work contains key details of the molecule’s structure, as well as information about how the LAG-3 protein functions.

Although over a dozen immunotherapies targeting LAG-3 are in development, and one is already FDA approved, knowledge of LAG-3’s structure and function has been incomplete.

“Given the amount of time and resources being put into developing therapeutics that target LAG-3, it is astounding that we don’t yet have a full understanding of how this protein functions,” said Jennifer Cochran , the Addie and Al Macovski Professor in the School of Engineering and professor of bioengineering, and co-senior author on the study detailing LAG-3, published in Proceedings of the National Academy of Sciences .

Getting a clear image of a protein might not seem like a big deal, but when it comes to proteins, form often begets function. If you know what a protein looks like at the atomic scale, you can begin to understand how it interacts with other molecules and design experiments to further deduce how it works. Studies like these are crucial to developing drugs that can optimally block their target’s function.

A key structure

Proteins like LAG-3, called immune checkpoints, exist to stop our immune system from attacking things they shouldn’t. In theory, our immune system should naturally recognize tumor cells as foreign. But a checkpoint protein shield can give cancer cover.

Current immunotherapies aren’t chemical drugs, they’re lab-manufactured antibodies that attach to certain parts of these checkpoints, and essentially turn them off. Once the checkpoint is turned off, our immune system can recognize and target the cancer again.

There are already approved antibody treatments that target two checkpoint proteins: CTLA-4 and PD-1. Both turn off our immune systems but in different ways. Because CTLA-4 and PD-1 were the first two checkpoint proteins found, they are quite well studied, and different approaches to inhibiting them for cancer therapy earned scientists the 2018 Nobel Prize in physiology or medicine.

LAG-3 seems to work in an entirely different way. Scientists hope that those differences might make it a better or complementary target to treat certain types of cancer, said Jack Silberstein, the Stanford immunology PhD student who co-led the work.

Because of that, Silberstein said, “there was all this excitement in the field. Groups rushed to make antibodies against LAG-3, without knowing entirely how LAG-3 or those antibodies functioned.”

Silberstein and colleagues, including those in Stanford’s Sarafan ChEM-H Macromolecular Structure Knowledge Center and the SLAC National Accelerator Laboratory , began working on LAG-3’s structure in 2019. A structure of LAG-3 was published by a different group in 2022 providing an initial glimpse of the protein, but it lacked crucial detail around sugar molecules that are key to LAG-3’s function, and detailed information on how the LAG-3 structure related to its biological activity.

A painstaking process

When Silberstein first started this project, “I quickly realized why there was no published structure. It’s a tremendously difficult protein to work with.”

And the technique Silberstein used to get the structure, called X-ray crystallography, is extremely finicky. First, Silberstein had to grow a crystal made entirely out of LAG-3 protein. Then, in collaboration with Irimpan Mathews at the SLAC National Accelerator Laboratory, they fired X-ray beams at the crystal to create a 3D image of the molecule using the Stanford Synchrotron Radiation Lightsource .

LAG-3 is a spindly, flexible protein, so it’s difficult to get the molecules to stack in an orderly way. Silberstein estimates he made more than 10,000 crystals, of which 3,000 were fired with X-rays before the team finally solved the structure.

“It was a very intense, grind-it-out-for-three-years, bang-your-head-against-the-wall kind of thing,” Silberstein said.

But it paid off. The team’s structure confirmed that LAG-3 exists as a dimer, with two LAG-3 molecules coming together to form the functional checkpoint protein. The sugar residue that was elusive in previous structural efforts is a key element in the LAG-3 dimer interface and helps promote a different orientation of the LAG-3 protein.

With the structure described, colleagues at New York University, including MD, PhD student Jasper Du and pathology Assistant Professor Jun Wang co-led critical experiments further elucidating LAG-3’s function. Other NYU colleagues, including Kun-Wei Chan and Xiang-Peng Kong, helped conduct electron microscopy studies to detail disruption of dimer formation by LAG-3 antibodies.

Additional work by the team uncovered, for the first time, that an antibody that has been used for close to 20 years to demonstrate therapeutic efficacy in animal tumor models blocks the activity of LAG-3 by binding to the interface between two LAG-3 molecules, disrupting LAG-3 from forming its functional dimer. Intriguingly, LAG-3 antibodies in clinical development bind to other areas of the protein, away from this dimer interface.

There will never be just one “cure,” because cancers are all different and involve a number of diverse biochemical pathways. Silberstein and Cochran envision a future where a tapestry of surgical, chemical, and immunological treatment approaches are employed, driven by basic science discoveries and medical innovations. Additional treatments targeting LAG-3 may very well be a part of that picture.

Additional Stanford co-authors are Jessica Frank, BS ’22 in bioengineering, MS ’23 in computer science; Irimpan Mathews, lead scientist at SLAC National Accelerator Laboratory; graduate students Yong Bin Kim, Phillip Liu, and Grayson Rodriguez; and Daniel Fernandez, director of crystallography at Sarafan ChEM-H . Additional co-authors are from New York University.

Cochran is also the senior associate vice provost for research and professor by courtesy, of chemical engineering. She is a member of Stanford Bio-X , the Cardiovascular Institute , the Maternal & Child Health Research Institute (MCHRI) , the Stanford Cancer Institute , and the Wu Tsai Neurosciences Institute , and a faculty fellow of Sarafan ChEM-H . Silberstein was a Bio-X Stanford Interdisciplinary Graduate Fellow during this work.

This work was funded by Stanford Bio-X, the National Institutes of Health, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an Enhancing Diversity in Graduate Education (EDGE) Fellowship, National Science Foundation graduate fellowships, a Cancer Research Institute Irvington Postdoctoral Fellowship, the Stanford Molecular Biophysics Training Program, a Stanford Graduate Fellowship in Science & Engineering, the NIH Melanoma Research Alliance, the V Foundation, the Mark Foundation, the NYU Colton Center for Autoimmunity, and the Emerson Collective Cancer Research Fund.

Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.

To read all stories about Stanford science, subscribe to the biweekly   Stanford Science Digest .

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Jill Wu, Stanford University School of Engineering: (386) 383-6061, [email protected]

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Cancer death rates continue to fall, driven by new treatments and improved screening

Significant strides in cancer treatments, diagnostic tools and prevention strategies continue to drive down cancer death rates, according to a report published Wednesday by the American Association for Cancer Research. 

Death rates from cancer have been falling over the past two decades, particularly sharply in recent years, the group's annual Cancer Progress Report found. As a result, there are now more than 18 million cancer survivors in the U.S. — up from 3 million in 1971.

“This is a really exciting time in cancer management,” said Dr. Stephen Ansell, the senior deputy director for the Midwest at the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota, who wasn’t involved with the report. “We see the death rate from cancer keeps going down.”

President Joe Biden relaunched his “Cancer Moonshot” initiative this year, and last week he outlined new steps to expand on the program.

The initiative expands funding for cancer research, especially immunotherapies. 

Dr. Lisa Coussens, the president of the American Association for Cancer Research, said: “You can’t stop funding basic science now with the belief that the current treatments will be good enough. Investing in basic science has a huge payoff to the public.” 

Harnessing the immune system to fight cancer

Coussens highlighted the growing use of immunotherapies as an example of how cancer treatments have improved. 

“Our ability to utilize or leverage the power of the immune system to fight cancer is huge,” Coussens said. “It’s why you are seeing much more significant survival rates in many cancers, such as lung and kidney cancers and melanoma.”

Immunotherapies use a person’s own immune system to fight off cancer.

“Cancer cells are mavericks, but they are your own cells. Your immune system is designed to not attack your own cells,” said Dr. Larry Norton, the medical director of the Evelyn H. Lauder Breast Center at the Memorial Sloan Kettering Cancer Center in New York. “But new drugs called immune checkpoint inhibitors allow your immune system to attack its own cancer cells.” 

The Food and Drug Administration approved the first immune checkpoint inhibitor in 2011 — a drug called ipilimumab, used for metastatic melanoma . Since then, it has approved eight other immune checkpoint inhibitors for 18 types of cancer, according to the report.

In March, the FDA approved the first new immune checkpoint inhibitor in eight years. The drug, called relatlimab, is used for melanoma.

In addition, the agency has approved seven other cancer therapeutics in the past year, including the first drug to treat uveal melanoma, the most common form of eye cancer in adults. It also expanded the use of 10 existing drugs to other cancers.

Coussens also highlighted developments in cancer drugs that work by targeting specific DNA mutations in cancer cells but noted that more work is still needed.

“The development of molecularly targeted drugs has certainly been a game-changer but haven’t been enough to result in true significant changes in overall survival,” she said.

Catching cancer early

Also key to cutting cancer death rates is catching the disease as early as possible.

“Early diagnosis is absolutely essential,” Coussens said. “A patient has the best odds of surviving a cancer diagnosis if it’s caught very early in a premalignant stage or before that primary tumor has spread to other body parts.”

Efforts to get more people to undergo routine screening for common cancers, such as breast, cervical, colon and prostate cancer, are making an impact. The Centers for Disease Control and Prevention’s Colorectal Cancer Control Program increased colorectal cancer screening rates by more than 12% in the past four years, according to the report. 

Researchers remain optimistic about so-called liquid biopsies — tests that would screen for cancer using a simple blood test , as opposed to a traditional imaging scan or biopsy. 

New research presented this month at ESMO 2022, a European cancer conference, showed promising data for the technique, called multi-cancer early detection blood testing. Scientists around the world are still honing the new diagnostic method, which is likely to play a huge role in the future of cancer diagnosis and treatment, Norton said. 

Equal access remains a challenge

Despite the progress in new therapies, racial disparities, managing preventable risk factors and getting people to schedule routine cancer screenings remain key hurdles in cancer care.

Black Americans still have the highest death rate and the shortest survival rate for most cancers of any racial or ethnic group. Hispanic Americans and American Indian Alaska Natives are also largely left out of the improvements in cancer management that white and Asian American Pacific Islanders have access to. 

“All of these advances are not being spread uniformly across the U.S. population,” Norton said.

New cancer therapies are often available only at specialized centers, which are difficult to access for people who don’t live near them and don’t have the means to travel for care. They also often require long hospital stays, which take people away from work and require extra money for lodging, Ansell said.

Minimally invasive surgical techniques that don’t require overnight stays in the hospital and novel therapies that can be administered at home, rather than in clinics, are in the works. Both could break down access barriers. 

“While it’s exciting to see the progress, there is so much additional work to be done,” Ansell said. “We aren’t done until we have beat cancer for everybody.” 

Follow  NBC HEALTH  on  Twitter  &  Facebook .

Kaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.

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Bladder cancer: Research is driving new treatment options, better outcomes

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Editor's note: May is Bladder Cancer Awareness Month.

By Jessica Saenz

Just 10 years ago, people with bladder cancer whose cancer had not spread and didn't respond to treatment often required bladder removal, says Mark Tyson, II, M.D. , a Mayo Clinic Comprehensive Cancer Center urologic surgeon. "Now, we have a whole host of new drugs and clinical trials that allow us to offer more options," he says. Many of these options provide effective treatment while preserving the bladder. And clinical trials can provide additional options.

Most bladder cancers are urothelial carcinomas, which begin in the urothelial cells lining the inside of your bladder. Most are also non-muscle-invasive, meaning they have not spread beyond the bladder's muscle wall. While treatment depends on cancer type, grade, stage, the patient's overall health and other factors, Dr. Tyson says "We are, hopefully, going to be able to keep the disease at bay for the vast majority of people."

Dr. Tyson talks about new and developing bladder cancer treatments and what you should know when seeking bladder cancer care:

Individualized treatments and improved techniques are producing better outcomes

Newly approved drug combination.

In 2023, the Food and Drug Administration (FDA) approved a two-drug combination of enfortumab vedotin and pembrolizumab (EV/pembro) to treat locally advanced or metastatic urothelial bladder cancer. The combination was previously only approved for the significant number of people who were ineligible for first-line treatment with a type of chemotherapy called cisplatin .

"Clinical trial results showed that EV/pembro was better than cisplatin and cisplatin-based combination chemotherapy in the first-line setting," says Dr. Tyson. Study results also highlighted a 55% reduction in disease progression or death compared to treatment with cisplatin-based chemotherapy, making EV/pembro the first treatment for urothelial bladder cancer to outperform chemotherapy when used as a first-line treatment.

"EV/pembro is now the new standard of care for patients with metastatic urothelial bladder cancer," says Dr. Tyson.

Single-port cystectomy (bladder removal surgery)

Cystectomy (bladder removal) might be recommended for muscle-invasive bladder cancer and for non-muscle-invasive bladder cancer that hasn't responded to other treatments or is likely to spread. It can be done with one large incision or several small incisions using minimally invasive surgery .

Dr. Tyson says Mayo Clinic is leading the way in refining a single-incision robotic surgery for bladder removal and reconstruction. This method shows potential for less pain, fewer postoperative complications and shorter hospital stays, although more research needs to be conducted.

Clinical trials testing new immunotherapy and less-invasive surveillance

Immunotherapy for treatment-resistant non-muscle-invasive bladder cancer.

Immunotherapy, a drug treatment that helps your immune system fight cancer, is sometimes used to prevent the recurrence of non-muscle-invasive bladder cancer, especially when bladder preservation is a priority. A current standard-of-care immunotherapy is Bacillus Calmette-Guérin (BCG) , a vaccine that uses weakened bacteria to stimulate the immune system to kill remaining cancer cells in the bladder. For high-grade, non-muscle-invasive bladder cancer that's unresponsive to BCG, a new immunotherapy called cretostimogene grenadenorepvec is on the fast track for FDA approval, says Dr. Tyson. Mayo Clinic is participating in a phase 3 clinical trial testing cretostimogene grenadenorepvec.

"We presented data at the annual meeting of the American Urological Association in 2024 showing promising results from a study conducted in patients with BCG-unresponsive, non-muscle-invasive bladder cancer," says Dr. Tyson. "As part of the trial, it's administered once a week for six weeks, and it's well tolerated, so patients don't have many side effects. Then we reassess them for three months, and if they've had a good response, they go on maintenance cretostimogene for three, six, nine, 12 and 18 months." Preliminary study results showed that out of 112 people who had completed the treatment course, 75.2% had a complete response, meaning that their cancer had not recurred. Eighty-three percent of complete responders who had one year of follow-up maintained their complete response beyond one year.

Urine test for non-muscle-invasive bladder cancer recurrence monitoring

Because bladder cancer has a high recurrence rate and can progress from non-muscle-invasive to muscle-invasive disease during treatment, surveillance is important. Post-treatment monitoring often involves cystoscopy , a procedure where a scope is inserted through the urethra — the tube that carries urine out of your bladder — to examine the inside of your bladder.

Intravesical therapy, chemotherapy given directly into the bladder through a tube passed through the urethra, is an option for people with non-muscle-invasive bladder cancer. "Patients undergoing intravesical therapy generally need surveillance cystoscopy every three to six months for a couple of years, every six months for a couple of years, and yearly thereafter," says Dr. Tyson.

Cystoscopies can be uncomfortable and sometimes painful, and Dr. Tyson says a less-invasive surveillance method might become an option for people after non-muscle-invasive bladder cancer treatment. "One of the exciting studies we're doing at Mayo Clinic uses a urinary biomarker from a urine sample to identify recurrence without the need for cystoscopy," he says. The study aims to learn about people's preferences, comfort level and confidence in the urine test compared to cystoscopy.

Finding the most effective bladder cancer treatment for you

Choosing bladder cancer treatment is a personal decision. There are many factors to consider, including bladder preservation and quality of life. Dr. Tyson says it's important to find an attentive care team that treats a high volume of people with bladder cancer and has expertise in different surgical approaches to treatment.

"Try to find a healthcare professional willing to spend time with you to answer your questions," says Dr. Tyson. "If you feel rushed, that's not a good thing. If you feel like your care team isn't talking to you about all the options available, you're not getting a good opinion." He says learning about and considering all the treatment options is especially important if you want to preserve your bladder.

Dr. Tyson also recommends talking to your healthcare team about bladder cancer clinical trials , which might be beneficial if your cancer continues to advance after treatment. "People should look for care at centers that offer clinical trials, especially if they have non-muscle-invasive disease. Clinical trials are a good opportunity to get next-generation therapies."

Bladder cancer treatment and survival have improved drastically over the last decade. Dr. Tyson wants people with bladder cancer to know they have more options than ever before.

"If you have non-muscle-invasive bladder cancer, you're unlikely to die from your disease, and it's becoming more unlikely that you will lose your bladder," he says. "For muscle-invasive bladder cancer, the landscape has totally changed with EV/pembro. There's a lot of reason for hope. There's a lot of reason to think you can beat this disease."

Learn more about  bladder cancer  and find a  clinical trial  at Mayo Clinic.

Join the Bladder Cancer Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Read these articles:

• Bladder cancer: What you should know about diagnosis, treatment and recurrence
• Bladder cancer patients require ongoing surveillance

Also, watch these videos:

• Mayo Clinic explains bladder cancer
• Dr. Mark Tyson answers questions about bladder cancer

Related Posts

Dr. Mark Tyson explains how bladder cancer experts tailor treatments to each person's cancer to improve outcomes and prevent recurrence.

In this Mayo Clinic Q&A podcast video, Dr. Mark Tyson discusses bladder cancer diagnosis, staging and treatment.

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Cancer therapy articles from across Nature Portfolio

Cancer therapy describes the treatment of cancer in a patient, often with surgery, chemotherapy and/or radiotherapy. Targeted therapies are also available for some cancer types. A cancer patient might receive many different types of therapy, including those aimed at relieving the symptoms of cancer, such as pain.

Overall survival with adjuvant pembrolizumab in renal cell carcinoma — the shock of the lightning

In the KEYNOTE-564 trial, patients with resected clear cell renal cell carcinoma at a high risk of relapse experienced disease-free survival and especially overall survival benefits following treatment with pembrolizumab, which in turn was established as the novel standard adjuvant therapy for these patients. Accurate patient selection is crucial. Managing post-pembrolizumab recurrence is challenging owing to limited evidence for guiding therapeutic decisions based on clinical features.

• Francesco Massari
• Matteo Rosellini
• Veronica Mollica

A milestone method to make natural killer T cells

A differentiation protocol to produce off-the-shelf natural killer T cells may enable clinical application.

• Leonid S. Metelitsa

Using single-cell transcriptomics to predict which tumors will respond to targeted therapy

We performed a proof-of-concept study showing that single-cell RNA sequencing, a method for capturing rich tumor information (not yet in clinics owing to high costs), can be used to identify patients likely to respond to targeted therapy and to monitor the emergence of resistance.

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• Cancer immunotherapy
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Cancer Treatments and Research

Learn more about the progress made in improving cancer survival rates

Cancer Treatment Development

Radiotherapy, immunotherapy, targeted therapy.

• Combination Therapies

Diagnostics

Considerable progress has been made in reducing cancer rates and improving cancer survival in the United States since the 1990s. A greater understanding of the immune system , genetics , and cancer pathology has opened the doors to an ever-increasing range of new cancer treatments and diagnostic tools.

Advances in cancer care have been highly specific in terms of the diagnostic and treatment modalities that are recommended for each type of cancer. This article will describe these key treatments as well as the process of cancer treatment development.

sanjeri / Getty Images

Throughout the years, there have been discoveries of drugs and treatment methods that prove to be more successful or reliable than previous ones. These treatment methods are discovered in different ways.

Some are found in nature through the testing and studying of plants, fungi, and animals. Others are found through the study of cancer cells and existing drugs or procedures. But before any type of treatment method is used on patients, there is an important process that ensures its safety and effectiveness.

New cancer drugs typically go through stages of clinical research. These stages are:

• Preclinical research : Preclinical research aims to ensure a form of treatment is safe for human use. Laboratory studies that include animal research and in vitro studies , or experiments usually done in test tubes and Petri dishes, are common in this research stage.
• Clinical research : After preclinical research is successful, clinical research focuses on testing the form of therapy on humans. This clinical research stage can be lengthy (up to 10 years or more) as the discovered treatment goes through phases of clinical trials .
• Post-clinical research : Post-clinical research involves studying a therapy that has gone through the clinical research phase and received approval for human use. This involves collecting data on effectiveness and safety in real-world use.

Advances in and refinement of cancer surgery—including the use of targeted drugs and other medications before and after surgery—that can improve outcomes for cancer patients continue to emerge.

Studies comparing the outcomes of different surgical methods have helped guide doctors in selecting the technique that is most likely to result in a better long-term prognosis.

Video-Assisted Thoracoscopic Surgery (VATS) Lobectomy for Lung Cancer

During a lobectomy , a portion of a lobe of a lung that is affected by cancer is removed.

The minimally invasive technique known as VATS lobectomy, done with general anesthesia , often involves a shorter recovery time than open surgery for lung cancer . The American College of Chest Physicians identifies VATS lobectomy as the preferred method for treating early-stage lung cancer.

During the procedure, a thoracoscope, which is a small tube with a light and camera attached to the end, is inserted between the ribs through a small incision. The affected lung tissue is then removed using special tools.

Open Surgery for Cervical Cancer

In a clinical trial between 2008 and 2013, 631 women were enrolled to compare the efficacy of open surgery with that of minimally invasive surgery for the treatment of cervical cancer .

Postoperative quality of life for both groups was similar. But open surgery resulted in lower rates of cancer recurrence and higher disease-free survival.

Another study found that patients with early-stage cervical cancer who had minimally invasive surgery experienced higher recurrence rates than those who had open surgery, making open surgery a better option for some patients.

Radiation therapy is used as an adjunct to cancer treatment. More effective and targeted radiotherapies are being used to treat early and advanced cancers.

Stereotactic Ablative Radiotherapy (SABR) for Metastatic Cancer

A study demonstrated that patients receiving SABR in addition to standard of care showed improved survival compared with patients receiving palliative standard of care.  

SABR for Inoperable Early-Stage Lung Cancer

For patients who are not surgical candidates, SABR offers an alternative. This approach was shown to have excellent local control and well tolerated in a cohort of 273 patients.

Immunotherapy uses the body's immune system to fight cancer. Immunotherapy can boost or change how the immune system works so it can find and attack cancer cells.  

Molecular testing, which can help select patients most suitable for immunotherapy, has opened the door to this newer form of treatment. Some of the early and commonly used immunotherapy agents are vaccines, including the first FDA-approved cancer vaccine, sipuleucel-T, for prostate cancer .

Below are some breakthrough agents grouped by category:

• Monoclonal antibodies , such as Trodelvy for metastatic triple-negative breast cancer
• Oncolytic virus therapy , including Imlygic for inoperable melanoma
• CAR T-cell therapy , such as CD22 for acute lymphoblastic leukemia relapse
• Cancer vaccines , such as Provenge for prostate cancer

Targeted therapy is when drugs are directed at specific proteins or genes that promote cancer cell growth. It is designed to attack cancer cells directly.

Some of the targeted drugs commonly used to treat cancer are Tagrisso (osimertinib), Tarceva (erlotinib), and Iressa (gefitinib) for lung cancer, and Kadcyla (ado-trastuzumab), Tykerb (lapatinib), and Afinitor (everolimus) for breast cancer.

Kinase Inhibitors

Dysregulation of protein kinases is involved in many types of cancer, and this protein is the target of several cancer drugs.

Drugs like Rozlytrek (entrectinib) and Tabrecta (capmatinib) are used to treat metastatic non-small cell lung cancer .

• Rozlytrek (entrectinib) is used to treat non-small cell lung cancer that is positive for ROS1 and the neurotrophic receptor tyrosine kinases (NTRK) fusion-positive solid tumors. It inhibits cell-proliferation while targeting ROS1, a receptor tyrosine kinase.
• Tabrecta (capmatinib) is a tyrosine kinase inhibitor that can help to shrink tumors involving a MET mutation. The MET gene produces a receptor tyrosine kinase, which is involved in cell proliferation and cell survival.

Kinase Inhibitor

Our bodies contain enzymes called kinases, which help to regulate functional processes such as cell signaling and cell division. A kinase inhibitor blocks the action of kinases.

PARP Inhibitors

Drugs, such as Zejula, are used to treat ovarian cancer . The drug inhibits the enzymatic activity of enzyme poly (ADP-ribose) polymerase (PARP). In a study of 533 patients who had recurring ovarian cancer, Zejula increased the time experienced without symptoms compared with standard therapy.

Combination Therapies 

Combination therapy means using two forms of cancer therapy in conjunction. Newer classes of drugs are being combined with traditional chemotherapy to improve outcomes. This approach becoming the standard of care for treating some types of cancer.

One recent example is the combination of Tecentriq and Avastin in the treatment of liver cancer.

It is an ongoing area of critical research to develop better and more accurate diagnostic and screening techniques. Below are some next-generation technologies that are being developed. However, keep in mind these techniques (aside from ctDNA) have yet to be approved by the FDA.

Artificial Intelligence Mammograms

In a study that involved 28,296 independent interpretations, AI performance was comparable to radiologists' diagnostic ability for detecting breast cancer.

Liquid Biopsy for Breast Cancer

A liquid biopsy can detect circulating levels of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA).

In a meta-analysis that included 69 published research studies. with 5,736 breast cancer patients, researchers determined that the status of ctDNA mutation predicts disease recurrence and adverse survival results. They also found that the levels of cfDNA can predict metastasis of the axillary lymph node.

Monarch Robotic Endoscopy for Lung Cancer

This may be advantageous for patients with external lung lesions that need biopsy prior to surgery, radiation, targeted therapies, or immunotherapy.  

Genomic Cancer Screening in Embryos

A polygenic risk score used by genomic prediction accurately distinguished which person in a set of siblings will inherit a medical condition. The accuracy was cited between 70% and 90%, depending upon the condition.  

At-Home Urine Test for Prostate Cancer

A convenient, at-home urine test can be used to detect extracellular vesicle-derived RNA to provide prognostic information for men under active surveillance for prostate cancer.   

A Word From Verywell

Cancer research that is investigating better treatments and diagnostic tools is ongoing. Even if you have advanced metastatic cancer, it may be comforting to know that newer treatments are being studied and approved every year. As treatments become better and better, your chances of survival and remission will also improve. If you have been diagnosed with cancer, it may also help to seek a cancer support group to boost your mental well-being and resilience.

American Society of Clinical Oncology: Cancer.Net. How are cancer drugs discovered and developed .

Cancer.net Improvements in Surgery for Cancer: The 2020 Advance of the Year.

Berfield KS, Farjah F, Mulligan MS. Video-assisted thoracoscopic lobectomy for lung cancer . Ann Thorac Surg. 2019 Feb;107(2):603-609. doi: 10.1016/j.athoracsur.2018.07.088

Frumovitz M, Obermair A, Coleman RL, Pareja R, Lopez A, Ribero R. Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (Lacc): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial . Lancet Oncol . 2020 Jun;21(6):851-860. doi: 10.1016/S1470-2045(20)30081-4

Kim SI, Cho JH, Seol A, et al. Comparison of survival outcomes between minimally invasive surgery and conventional open surgery for radical hysterectomy as primary treatment in patients with stage IB1-IIA2 cervical cancer .  Gynecol Oncol . 2019;153(1):3-12. doi:10.1016/j.ygyno.2019.01.008

Palma DA, Olson R, Harrow S, Gaede S, Louie A, Haasbeek C. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (Sabr-comet): a randomised, phase 2, open-label trial. Lancet. 2019 May 18;393(10185):2051-2058. doi: 10.1016/S0140-6736(18)32487-5

Murray L, Ramasamy S, Lilley J, et al. Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort .  Clin Oncol (R Coll Radiol) . 2016;28(1):4-12. doi:10.1016/j.clon.2015.09.007

American Cancer Society. Immunotherapy .

Sastre J, Sastre-Ibañez M. Molecular diagnosis and immunotherapy . Curr Opin Allergy Clin Immunol . 2016 Dec;16(6):565-570. doi: 10.1097/ACI.0000000000000318

Vansteenkiste JF, Van De Kerkhove C, Wauters E, Van Mol P. Capmatinib for the treatment of non-small cell lung cancer.   Expert Rev Anticancer Ther . 2019;19(8):659-671. doi:10.1080/14737140.2019.1643239

Matulonis UA, Walder L, Nøttrup TJ, et al. Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial .  J Clin Oncol . 2019;37(34):3183-3191. doi:10.1200/JCO.19.00917

Breast Cancer Research Foundation. How Combination Therapies Are Changing the Landscape of Breast Cancer Care .

Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma .  N Engl J Med . 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745

Rodriguez-Ruiz A, Lång K, Gubern-Merida A, et al. Stand-Alone Artificial Intelligence for Breast Cancer Detection in Mammography: Comparison With 101 Radiologists .  J Natl Cancer Inst . 2019;111(9):916-922. doi:10.1093/jnci/djy222

Alimirzaie S, Bagherzadeh M, Akbari MR. Liquid biopsy in breast cancer: A comprehensive review . Clin Genet . 2019 Jun;95(6):643-660. doi: 10.1111/cge.13514

Murgu SD. Robotic assisted-bronchoscopy: technical tips and lessons learned from the initial experience with sampling peripheral lung lesions. BMC Pulm Med. 2019 May 9;19(1):89. doi: 10.1186/s12890-019-0857-z

Lello L, Raben TG, Hsu SDH. Sibling validation of polygenic risk scores and complex trait prediction.   Sci Rep 10 ,  13190 (2020). doi.org/10.1038/s41598-020-69927-7

Connell SP, Hanna M, McCarthy F, et al. A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients [published online ahead of print, 2019 May 20].  BJU Int . 2019;124(4):609-620. doi:10.1111/bju.14811

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Innovative approaches for cancer treatment: current perspectives and new challenges

Carlotta pucci.

1 Smart Bio-Interfaces, Istituto Italiano di Tecnologia, 56025 Pisa, Italy

a https://orcid.org/0000-0002-8976-3711

Chiara Martinelli

b https://orcid.org/0000-0001-9360-1689

Gianni Ciofani

2 Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Torino, Italy

c https://orcid.org/0000-0003-1192-3647

Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research.

Introduction

Cancer is one of the main causes of death worldwide, and in the past decade, many research studies have focused on finding new therapies to reduce the side effects caused by conventional therapies.

During cancer progression, tumours become highly heterogeneous, creating a mixed population of cells characterised by different molecular features and diverse responsivity to therapies. This heterogeneity can be appreciated both at spatial and temporal levels and is the key factor responsible for the development of resistant phenotypes promoted by a selective pressure upon treatment administration [ 1 ]. Usually, cancer is treated as a global and homogeneous disease and tumours are considered as a whole population of cells. Thus, a deep understanding of these complex phenomena is of fundamental importance in order to design precise and efficient therapies.

Nanomedicine offers a versatile platform of biocompatible and biodegradable systems that are able to deliver conventional chemotherapeutic drugs in vivo , increasing their bioavailability and concentration around tumour tissues, and improving their release profile [ 2 ]. Nanoparticles can be exploited for different applications, ranging from diagnosis to therapy [ 2 ].

Recently, extracellular vesicles (EVs), responsible for cancer development, microenvironment modification and required for metastatic progression, have been widely investigated as efficient drug delivery vehicles [ 3 ].

Natural antioxidants and many phytochemicals have been recently introduced as anti-cancer adjuvant therapies due to their anti-proliferative and pro-apoptotic properties [ 4 , 5 ].

Targeted therapy is another branch of cancer therapy aiming at targeting a specific site, such as tumour vasculature or intracellular organelles, leaving the surroundings unaffected. This enormously increases the specificity of the treatment, reducing its drawbacks [ 6 ].

Another promising opportunity relies on gene therapy and expression of genes triggering apoptosis [ 7 ] and wild type tumour suppressors [ 8 ], or the targeted silencing mediated by siRNAs, currently under evaluation in many clinical trials worldwide [ 9 ].

Thermal ablation of tumours and magnetic hyperthermia are opening new opportunities for precision medicine, making the treatment localised in very narrow and precise areas. These methods could be a potential substitute for more invasive practices, such as surgery [ 10 , 11 ].

Furthermore, new fields such as radiomics and pathomics are contributing to the development of innovative approaches for collecting big amounts of data and elaborate new therapeutic strategies [ 12 , 13 ] and predict accurate responses, clinical outcome and cancer recurrence [ 14 – 16 ].

Taken all together, these strategies will be able to provide the best personalised therapies for cancer patients, highlighting the importance of combining multiple disciplines to get the best outcome.

In this review, we will provide a general overview of the most advanced basic and applied cancer therapies, as well as newly proposed methods that are currently under investigation at the research stage that should overcome the limitation of conventional therapies; different approaches to cancer diagnosis and therapy and their current status in the clinical context will be discussed, underlining their impact as innovative anti-cancer strategies.

Nanomedicine

Nanoparticles are small systems (1–1,000 nm in size) with peculiar physicochemical properties due to their size and high surface-to-volume ratio [ 17 ]. Biocompatible nanoparticles are used in cancer medicine to overcome some of the issues related to conventional therapies, such as the low specificity and bioavailability of drugs or contrast agents [ 2 ]. Therefore, encapsulation of the active agents in nanoparticles will increase their solubility/biocompatibility, their stability in bodily fluids and retention time in the tumour vasculature [ 18 – 20 ]. Furthermore, nanoparticles can be engineered to be extremely selective for a precise target [ 21 , 22 ] (see the “Targeted therapy and immunotherapy” section) and to release the drug in a controlled way by responding to a specific stimulus [ 18 , 23 – 25 ]. This is the case of ThermoDox, a liposomal formulation that can release doxorubicin as a response to an increment of temperature [ 26 ].

Inorganic nanoparticles are generally used as contrast agents for diagnosis purposes. Among them, quantum dots are small light-emitting semiconductor nanocrystals with peculiar electronic and optical properties, which make them highly fluorescent, resistant to photobleaching and sensitive for detection and imaging purposes [ 27 ]. Combined with active ingredients, they can be promising tools for theranostic applications [ 27 ]. In a recent study, quantum dots coated with poly(ethylene glycol) (PEG) were conjugated to anti-HER2 antibody and localised in specific tumour cells [ 28 ].

Superparamagnetic iron oxide nanoparticles (SPIONs) are usually exploited as contrast agents in magnetic resonance imaging (MRI) because they interact with magnetic fields [ 29 , 30 ]. Five types of SPIONs have been tested for MRI: ferumoxides (Feridex in the US, Endorem in Europe), ferucarbotran (Resovist), ferucarbotran C (Supravist, SHU 555 C), ferumoxtran-10 (Combidex) and NC100150 (Clariscan). Ferucarbotran is currently available in few countries, while the others have been removed from the market [ 25 ]. SPIONs have also been studied for cancer treatment by magnetic hyperthermia (see the “Thermal ablation and magnetic hyperthermia” section), and a formulation of iron oxide coated with aminosilane called Nanotherm has been already approved for the treatment of glioblastoma [ 31 ].

Gold nanoparticles have raised interest because of their optical and electrical properties and low toxicity [ 32 – 34 ]. They are mainly used as contrast agents for X-ray imaging, computed tomography [ 25 ], photoacoustic imaging [ 35 ] and photodynamic therapy [ 36 ]. A nanoshell made of a silica core and a gold shell coated with PEG was approved by the Food and Drug Administration (FDA) in 2012 and commercialised as AuroShell (Nanospectra) for the treatment of breast cancer by photodynamic therapy [ 25 ].

Organic nanoparticles are mainly used as delivery systems for drugs. Liposomes and micelles are both made of phospholipids, but they differ in their morphology. Liposomes are spherical particles having at least one lipid bilayer, resembling the structure of cell membranes. They are mainly used to encapsulate hydrophilic drugs in their aqueous core, but hydrophobic drugs can also be accommodated in the bilayer or chemically attached to the particles [ 37 ]. Micelles, instead, own a hydrophobic core that can encapsulate hydrophobic drugs [ 38 ]. Doxil, doxorubicin-loaded PEGylated liposomes, were the first nanoparticles approved by the FDA in 1995 to treat AIDS-associated Kaposi’s sarcoma [ 39 ]. This formulation drastically reduces doxorubicin side effects. Since then, other liposomal formulations have been approved by the FDA for cancer therapy, such as Myocet and DaunoXome [ 40 – 42 ]. Polymeric nanoparticles are made of biocompatible or natural polymers, such as poly(lactide-co-glycolide), poly(ε-caprolactone), chitosan, alginate and albumin [ 43 ]. Some formulations have already been accepted by the FDA, such as Abraxane (albumin-paclitaxel particles for the treatment of metastatic breast cancer and pancreatic ductal adenocarcinoma) and Ontak (an engineered protein combining interleukin-2 and diphtheria toxins for the treatment of non-Hodgkin’s peripheral T-cell lymphomas).

As well as these systems, which have been either accepted or are under clinical investigation, it is worth mentioning some new nanoparticles currently undergoing testing at the research level, which should improve treatment performance. For example, solid lipid nanoparticles, made of lipids that are solid at body temperature [ 44 ], and fabricated to load hydrophobic drugs [ 45 ] have been demonstrated to give a higher drug stability and prolonged release compared to other systems; however, the encapsulation efficiency is often low because of their high crystallinity [ 46 ]. To overcome this issue, one or more lipids, liquid at room temperature (like oleic acid, for example), are included in the formulation [ 47 ]. Lipid nanoparticles are good candidates for brain tumour therapy as they are able to cross the blood–brain barrier (BBB) [ 48 ]. A recent work showed that lipid nanoparticles loaded with SPIONs and temozolomide are efficient to treat glioblastoma since they combine the effect of the conventional chemotherapy and hyperthermia [ 49 , 50 ]. Dendrimers are another family of nanoparticles composed of polymers with a repetitive branched structure and characterised by a globular morphology [ 51 , 52 ]. Their architecture can be easily controlled, making their structure extremely versatile for many applications. For example, some recent studies show that poly-L-lysine (PLL) dendrimers loaded with doxorubicin induce anti-angiogenic responses in in vivo tumour models [ 53 ]. Currently, there is only one clinical trial for a formulation named ImDendrim based on a dendrimer and on a rhenium complex coupled to an imidazolium ligand, for the treatment of inoperable liver cancers that do not respond to conventional therapies [ 54 ].

Extracellular vesicles for cancer diagnosis and therapy

EVs are classified in two categories based on their biogenesis. Specifically, exosomes are small vesicles of around 30–150 nm originated from endosomes in physiological and pathological conditions and released by a fusion of multivesicular bodies (MVBs) to the cell membrane [ 55 , 56 ], while shed microvesicles (sMVs), with a typical size of 50–1,300 nm, are present in almost any extracellular bodily fluid and are responsible for the exchange of molecular materials between cells [ 57 , 58 ]. Exosomes are involved in cancer development and spreading [ 3 , 59 , 60 ], in the bidirectional communication between tumour cells and surrounding tissues, and in the construction of the microenvironment needed for pre-metastatic niche establishment and metastatic progression [ 61 ]. Hence, circulating vesicles are clinically relevant in cancer diagnosis, prognosis and follow up. Exosomes are actually recognised as valid diagnostic tools, but they can also be isolated and exploited as anti-cancer vaccines or nanosized drug carriers in cancer therapy [ 62 ].

Nowadays, one of the main issues in cancer diagnosis is the early identification of biomarkers by non-invasive techniques. Obtaining a significant amount of information, before and during tumour treatment, should allow the monitoring of cancer progression and the efficacy of therapeutic regimens. Liquid biopsies to detect circulating tumour cells, RNAs, DNAs and exosomes have been used as indicators for personalised medicine [ 63 ]. In recent years, exosomes detection has been validated as a reliable tool for preclinical practice in different cancer types [ 64 ], thanks to the identification of their content: double-stranded DNA (dsDNA) [ 65 , 66 ], messenger RNA (mRNA), micro RNA (miRNA), long non-coding RNA (lncRNA) [ 67 ], proteins and lipids [ 68 ]. DsDNA has been detected in exosomes isolated from plasma and serum of different cancer cell types, and mutated genes involved in tumorigenesis, such as mutated KRAS and TP53 [ 69 , 70 ], have been identified as disease predictors. Similarly, exosomal AR-V7 mRNA has been used as a prognostic marker of resistance to hormonal therapy in metastatic prostate cancer patients [ 71 ]. Gene expression profiling of multiple RNAs from urinary exosomes has been adopted as an efficient diagnostic tool [ 72 ]. LncRNAs isolated from serum exosomes have been exploited for disease prognosis in colorectal cancer patients [ 73 ], and multiple miRNAs allow one to distinguish between different lung cancer subtypes [ 74 ]. GPC1-positive exosomes have been employed to detect pancreatic cancer [ 75 ], while circulating exosomal macrophage migration inhibitory factor (MIF) was able to predict liver metastasis onset [ 76 ]. Finally, multiple lipids present in urinary exosomes have been approved as prostate cancer indicators [ 77 ]. Due to the high variability of patient classes and sample size, and in order to obtain clinically significant results for a fast and effective diagnosis, huge investments in exosome research will be required in the near future.

Exosomes could also be exploited as natural, biocompatible and low immunogenic nanocarriers for drug delivery in cancer therapy. They can be passively loaded by mixing purified vesicles with small drugs [ 78 – 82 ], or actively loaded by means of laboratory techniques, such as electroporation and sonication [ 83 , 84 ]. Superparamagnetic nanoparticles conjugated to transferrin have been tested for the isolation of exosomes expressing transferrin receptor from mice blood. After incubation with doxorubicin, they have been used to target liver cancer cells in response to external magnetic fields, inhibiting cell growth both in vitro and in vivo [ 80 ]. Kim et al. [ 83 ] engineered mouse macrophage-derived exosomes with aminoethyl anisamide-PEG to target sigma receptor, overexpressed in lung cancer cells and passively loaded them with paclitaxel. These systems acted as targeting agents able to suppress metastatic growth in vivo .

Three clinical trials with loaded exosomes are currently ongoing for the treatment of different tumours [ 85 – 87 ]: a phase I trial is evaluating the ability of exosomes to deliver curcumin to normal and colon cancer tissues [ 85 ]; a phase II trial is investigating the in vivo performance of autologous tumour cell-derived microparticles carrying methotrexate in lung cancer patients [ 86 ] and a clinical inquiry is focusing on autologous erythrocyte-derived microparticles loaded with methotrexate for gastric, colorectal and ovarian cancer treatment [ 87 ].

Recently, new strategies to produce ad hoc exosomes have been developed. Cells releasing exosomes have been genetically engineered to overexpress specific macromolecules, or modified to release exosomes with particular targeting molecules [ 88 – 90 ].

Exosomes derived from different cancer cells have already been exploited as cancer vaccines. Autologous dendritic cell-derived exosomes with improved immunostimulatory function have been tested in a phase II clinical trial for the activation of CD8 + T cells [ 91 ] in non-small cell lung cancer (NSCLC) patients, observing disease stabilisation and a better overall survival [ 92 ]. In a phase I trial, ascites-derived exosomes supplemented with granulocyte-macrophage colony stimulating factor (GM-CSF) have been administered to colorectal cancer patients, soliciting a tumour-specific immune response [ 93 ].

Many issues related to exosomes clinical translation remain open and are mostly connected to the definition of preclinical procedures for isolation, quantification, storage and standard protocols for drug loading. It is becoming even more necessary to distinguish between tumour and healthy blood cell-derived vesicles to characterise their post-isolation half-life and to perform standard content analyses. For these purposes, innovative approaches and technologies have been set up, such as microarrays and specific monoclonal antibodies and RNA markers amplification strategies [ 94 ].

Natural antioxidants in cancer therapy

Every day, the human body undergoes several exogenous insults, such as ultraviolet (UV) rays, air pollution and tobacco smoke, which result in the production of reactive species, especially oxidants and free radicals, responsible for the onset of many diseases, including cancer. These molecules can also be produced as a consequence of clinical administration of drugs, but they are also naturally created inside our cells and tissues by mitochondria and peroxisomes, and from macrophages metabolism, during normal physiological aerobic processes.

Oxidative stress and radical oxygen species are able to damage DNA (genetic alterations, DNA double strand breaks and chromosomal aberrations [ 95 , 96 ]) and other bio-macromolecules [ 97 ], such as lipids (membrane peroxidation and necrosis [ 98 ]) and proteins (significantly changing the regulation of transcription factors and, as a consequence, of essential metabolic pathways [ 99 ]).

The protective mechanisms our body has developed against these molecules are sometimes insufficient to counteract the huge damages produced. Recently, in addition to research into the roles of the physiological enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GP), natural antioxidants such as vitamins, polyphenols and plant-derived bioactive compounds are being studied in order to introduce them as preventive agents and potential therapeutic drugs [ 100 , 101 ]. These molecules have anti-inflammatory and anti-oxidant properties and are found in many vegetables and spices [ 102 ]. Vitamins, alkaloids, flavonoids, carotenoids, curcumin, berberine, quercetin and many other compounds have been screened in vitro and tested in vivo , displaying appreciable anti-proliferative and pro-apoptotic properties, and have been introduced as complementary therapies for cancer [ 4 , 5 , 103 ].

Despite the advantages of using natural drugs, their translation into clinical practice remains difficult due to their limited bioavailability and/or toxicity. Curcumin, a polyphenolic compound extracted from turmeric ( Curcuma longa ), is a traditional Southeast Asian remedy with anti-inflammatory, anti-oxidant and chemopreventive and therapeutic activities [ 104 ]. It has been shown to have cytotoxic effects in different kinds of tumours, such as brain, lung, leukaemia, pancreatic and hepatocellular carcinoma [ 105 , 106 ], with no adverse effects in normal cells at the effective therapeutic doses [ 107 ]. Curcumin can modulate a plethora of cellular mechanisms [ 108 , 109 ]; however, its biological properties, and as a consequence, the treatment duration and the efficient therapeutic doses, have not been completely elucidated yet. This molecule is highly lipophilic, poorly soluble in water and not very stable [ 110 ]. Different strategies and specific carriers, such as liposomes and micelles [ 111 , 112 ], have been developed to improve its bioavailability. Currently, 24 clinical trials involving curcumin are ongoing and 23 have been already completed [ 113 ].

Berberine is an alkaloid compound extracted from different plants, such as Berberis . Recently, it has been demonstrated to be effective against different tumours and to act as a chemopreventive agent, modulating many signalling pathways [ 114 , 115 ]. Like curcumin, it is poorly soluble in water; therefore, different nanotechnological strategies have been developed to facilitate its delivery across cell membranes [ 116 – 119 ]; six clinical trials are open and one has been completed [ 120 ].

Quercetin, a polyphenolic flavonoid found in fruits and vegetable, has been proven to be effective to treat several tumours, such as lung, prostate, liver, colon and breast cancers [ 121 – 123 ], by binding cellular receptors and interfering with many signalling pathways [ 124 ]. Interestingly, it has been shown to be effective also in combination with chemotherapeutic agents [ 125 ]. Presently, seven clinical trials are open and four have been completed [ 126 ].

Targeted therapy and immunotherapy

One of the main problems of conventional cancer therapy is the low specificity of chemotherapeutic drugs for cancer cells. In fact, most drugs act both on healthy and diseased tissues, generating severe side effects. Researchers are putting a lot of effort into finding a way to target only the desired site. Nanoparticles have raised great interest for their tendency to accumulate more in tumour tissues due to the enhanced permeability and retention effect (EPR) [ 127 ]. This process, called passive targeting, relies on the small size of nanoparticles and the leaky vasculature and impaired lymphatic drainage of neoplastic tissues [ 6 ]. Passive targeting, however, is difficult to control and can induce multidrug resistance (MDR) [ 128 ]. Active targeting, on the other hand, enhances the uptake by tumour cells by targeting specific receptors that are overexpressed on them [ 129 , 130 ]. Nanoparticles, for example, can be functionalized with ligands that univocally bind particular cells or subcellular sites [ 6 ]. Several kinds of ligands can be used, such as small molecules, peptides, proteins, aptamers and antibodies.

Folic acid and biotin are small molecules, whose receptors are overexpressed in tumour tissues. Several nanocarriers have been functionalized with folic acid to target ovarian and endometrial cancers [ 131 ]: folic acid-conjugated polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles delivering docetaxel increased drug cellular uptake by human cervical carcinoma cells [ 132 ]. Small ligands are cheap and can be linked to nanoparticles by simple conjugation chemistry [ 133 , 134 ].

Different kinds of small peptides and proteins are also effective in active targeting. Angiopep-2 is a peptide that has raised great interest in the treatment of brain cancer [ 135 ], because it binds to low-density lipoprotein receptor-related protein-1 (LRP1) of endothelial cells in the BBB, and it is also overexpressed in glioblastoma cancer cells [ 136 ]. Bombesin peptide conjugated to poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with docetaxel was used to target the gastrin-releasing peptide receptor, overexpressed on cell surface of prostate, breast, ovarian, pancreatic and colorectal cancer cells [ 137 , 138 ]. Transferrin is a serum glycoprotein overexpressed on many solid tumours, especially on glioblastoma multiforme cells [ 139 ], and on epithelial cells of the BBB [ 6 , 140 ]. Transferrin-conjugated chitosan-PEG nanoparticles delivering paclitaxel exhibited a higher cytotoxicity towards transferrin-overexpressing human non-small cell lung cancer cells (NSCLCs) (HOP-62) [ 141 ].

Aptamers are small synthetic single-stranded RNA or DNA oligonucleotides folded into specific shapes that make them capable of binding specific targets [ 142 ]. Farokhzad et al. [ 143 ] reported that the use of A10 RNA aptamer conjugated to docetaxel-loaded nanoparticles significantly enhances in vitro cytotoxicity. The same aptamer has been also used to prepare quantum dot-doxorubicin conjugates [ 144 ].

Antibodies are currently the most exploited ligands for active targeting. These proteins have a typical ‘Y’ shape, where the two arms are responsible for the selective interaction with the antigen [ 145 ]. Antibodies can be used as immunoconjugates, when conjugated to a drug or nanoparticle, or naked. In the first case, their function is mainly to target a specific antigen overexpressed on cancer cells. Antibodies used for this purpose include those ones that bind to the human epidermal growth factor receptor 2 (HER2), the epidermal growth factor receptor (EGFR), the transferrin receptor (TfR) and the prostate-specific membrane antigen (PSMA) [ 6 ]. Rapamycin-PLGA nanoparticle conjugated to EGFR antibody exhibited higher cellular uptake by human breast adenocarcinoma cells (MCF-7), with enhanced apoptotic activity [ 146 ]. Loperamide-loaded human serum albumin nanoparticles conjugated to antibodies that specifically bind transferrin receptor successfully crossed the BBB and delivered the drug to the desired site [ 147 ].

Naked antibodies or immunoconjugates can also be used in immunotherapy, which is a cancer treatment that aims at stimulating or restoring the immune system of the patient against cancer cells [ 148 ]. Antibodies can act as markers for cancer cells to make them more vulnerable to the immune system response (non-specific immune stimulation), or as inhibitors for immune checkpoint proteins on cancer cell surface, that can modulate the action of T-cells [ 148 ]. Several antibodies have been already tested and accepted by FDA for immunotherapy, such as rituximab (1997, [ 149 ]), ibritumomab tiuxetan (2002, [ 150 ]), trastuzumab emtansine (2013, [ 151 ]), nivolumab (2014, [ 152 ]) and pembrolizumab (2014, [ 153 ]).

Immunotherapy can be achieved by another strategy called adoptive cell transfer (ACT) and it consists of isolating T-lymphocytes (T-cells) with the highest activity against cancer directly from the patient’s blood, expanding them ex vivo , and reinfusing them again into the patient [ 154 ]. Autologous T-cells can be genetically engineered in vitro to express a chimaeric antigen receptor (CAR), which makes them more specific against cancer cell antigens [ 148 ]. Different CARs can be designed to be directed against a certain cancer antigen. The genetic modification of T-cells can be achieved by different methods such as viral transduction, non-viral methods like DNA-based transposons, CRISPR/Cas9 or other plasmid DNA and mRNA transfer techniques (i.e., electroporation, encapsulation in nanoparticles) [ 155 ]. ACT protocols have been already adopted in clinical practice for advanced or recurrent acute lymphoblastic leukaemia and for some aggressive forms of non-Hodgkin’s lymphoma [ 148 ]. For example, it has been shown that the treatment of end-stage patients affected by acute lymphocytic leukaemia with CAR T-cells led to a full recovery in up to 92% of patients [ 155 ]. Despite these very promising results, much research is currently devoted to understanding the long-term side effects of CAR T-cell therapies and their fate within tumours, and to improving CAR T-cell expansion technologies.

Gene therapy for cancer treatment

Gene therapy is intended as the introduction of a normal copy of a defective gene in the genome in order to cure specific diseases [ 156 ]. The first application dates back to 1990 when a retroviral vector was exploited to deliver the adenosine deaminase (ADA) gene to T-cells in patients with severe combined immunodeficiency (SCID) [ 157 ]. Further research demonstrated that gene therapy could be applied in many human rare and chronic disorders and, most importantly, in cancer treatment. Approximately 2,900 gene therapy clinical trials are currently ongoing, 66.6% of which are related to cancer [ 158 ]. Different strategies are under evaluation for cancer gene therapy: 1) expression of pro-apoptotic [ 159 , 160 ] and chemo-sensitising genes [ 4 ]; 2) expression of wild type tumour suppressor genes [ 5 ]; 3) expression of genes able to solicit specific antitumour immune responses and 4) targeted silencing of oncogenes.

One approach relied on thymidine kinase (TK) gene delivery, followed by administration of prodrug ganciclovir to activate its expression and induce specific cytotoxicity [ 161 ]. This has been clinically translated for the treatment of prostate cancer and glioma [ 162 – 164 ]. In recent decades, different vectors carrying the p53 tumour suppressor gene have been evaluated for clinical applications. ONYX-015 has been tested in NSCLC patients and gave a high response rate when administered alone or together with chemotherapy [ 165 ]. Gendicine, a recombinant adenovirus carrying wild-type p53 in head and neck squamous cell cancer had a similar success, inducing complete disease regression when combined with radiotherapy [ 166 ].

Despite many achievements, there are still some challenges to face when dealing with gene therapy, such as the selection of the right conditions for optimal expression levels and the choice of the best delivery system to univocally target cancer cells. Gene therapy also presents some drawbacks linked to genome integration, limited efficacy in specific subsets of patients and high chances of being neutralised by the immune system. Therefore, particular interest has been elicited by targeted gene silencing approaches.

RNA interference (RNAi) has been recently established as an efficient technology both for basic research and medical translation. Small interfering RNAs (siRNAs) consist of double-stranded RNAs [ 167 ] able to produce targeted gene silencing. This process is intracellularly mediated by the RNA-induced silencing complex (RISC), responsible for cleaving the messenger RNA (mRNA), thus leading to interference with protein synthesis [ 168 ]. This physiological mechanism has been demonstrated in many eukaryotes, including animals. A few years after RNAi discovery, the first clinical application for wet-age related macular degeneration treatment entered phase I clinical trial [ 169 ]. Since cancer is triggered by precise molecular mechanisms, siRNAs can be rationally designed to block desired targets responsible for cell proliferation and metastatic invasion. This strategy relies on siRNA-mediated gene silencing of anti-apoptotic proteins [ 170 ], transcription factors (i.e., c-myc gene) [ 171 , 172 ] or cancer mutated genes (i.e., K-RAS ) [ 173 ]. Most of the clinical trials currently ongoing are based on local administration of siRNA oligonucleotides in a specific tissue/organ or on systemic delivery throughout the entire body [ 9 , 174 ]. Using siRNA-based drugs has several advantages: 1) safety, since they do not interact with the genome; 2) high efficacy, because only small amounts can produce a dramatic gene downregulation; 3) possibility of being designed for any specific target; 4) fewer side effects when compared to conventional therapies and 5) low costs of production [ 175 , 176 ]. However, siRNAs are relatively unstable in vivo and can be phagocytosed during blood circulation, excreted by renal filtration, or undergo enzymatic degradation [ 177 ]. Occasionally, they can induce off-target effects [ 178 ] or elicit innate immune responses, followed by specific inflammation [ 179 , 180 ]. Since naked siRNAs are negatively charged hydrophilic molecules, they cannot spontaneously cross cell membranes. Consequently, different delivery strategies are currently under study, such as chemical modification, encapsulation into lipid or polymeric carriers or conjugation with organic molecules (polymers, peptides, lipids, antibodies, small molecules [ 181 ], for efficient targeting [ 182 , 183 ]). Chemical modifications include the insertion of a phosphorothioate at 3’ end to reduce exonuclease degradation [ 184 ], the introduction of 2’ O-methyl group to obtain longer half-life in plasma [ 185 ] and the modification by 2,4-dinitrophenol to favour membrane permeability [ 186 ]. Nevertheless, the degradation of modified siRNAs often elicits cytotoxic effects; therefore, it is preferable to design ad hoc nanocarriers.

Different cationic lipid nanoparticles, such as liposomes, micelles and solid lipid nanoparticles [ 183 ], have been exploited for siRNA loading. Cationic liposomes interact with negatively charged nucleic acids, which can be easily transfected by simple electrostatic interactions [ 187 , 188 ]. They can be constituted by 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and N-{1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl sulphate (DOTMA) [ 189 ]. A theranostic agent consisting of an anticancer survivin siRNA entrapped in PEGylated liposomes has been developed to achieve simultaneous localisation inside tumour cells by means of entrapped MR agents and fluorophores and reduction of proliferation in vivo [ 190 ].

Neutral liposomes based on 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) have shown high efficacy in mice models of ovarian carcinoma and colorectal cancer [ 191 , 192 ]. A phase I clinical trial is currently recruiting patients for evaluating the safety of siRNA-EphA2-DOPC when administered to patients with advanced and recurrent cancer [ 193 ].

Stable nucleic acid lipid particles (SNALPs) have been evaluated in non-human primates [ 194 ]. SiRNAs have been encapsulated in a mixture of cationic lipids coated with a shell of polyethylene glycol (PEG) [ 195 ]. SNALPs entered a phase I clinical trial in patients affected by advanced solid tumours with liver involvement [ 196 ] and a phase I/II trial for treating neuroendocrine tumours and adrenocortical carcinoma patients refractory to standard therapy [ 197 ].

SiRNAs can be condensed in cationic polymers such as chitosan, cyclodextrin and polyethylenimine (PEI). Chitosan is a natural polysaccharide that, due to its cationic charge, has been exploited as carrier for nucleic acids in vitro and in vivo [ 198 ]. Specifically, a targeted siRNA has been delivered in mice xenografts of breast cancer [ 199 ]. Cyclodextrin polymers coated with PEG, conjugated with human transferrin and carrying a siRNA called CALAA-01, inhibit tumour growth by reducing the expression of M2 subunit of ribonucleotide reductase (R2), and have entered a phase I clinical trial [ 200 ]. PEI is able to form small cationic nanoparticles containing siRNAs and it has been exploited as antitumoural, upon loading with HER-2 receptor-specific siRNA [ 201 ]. A phase II clinical trial is presently starting to evaluate siG12D LODER directed to mutated KRAS oncogene and encapsulated into a biodegradable polymeric matrix for locally treating advanced pancreatic cancer patients in combination with chemotherapy [ 202 ].

SiRNAs may be conjugated to peptides, antibodies and aptamers in order to improve their stability during circulation and to enhance cellular uptake [ 203 ]. A success is represented by siRNAs targeting PSMA, overexpressed in this type of cancer [ 204 ].

The introduction of nanocarriers has largely improved siRNAs stability, pharmacokinetics and biodistribution properties, and the targeting specificity [ 205 , 206 ]. Smart nanomaterials responsive to external (i.e., magnetic field, ultrasounds) and tumour-specific stimuli (i.e., acidic pH, redox conditions) are currently under the development for controlled release and reduction of undesired negative effects [ 207 , 208 ]. Nanocarriers delivering siRNAs undergo a series of pH variations from blood circulation to intracellular environment and, for this reason, many pH responsive materials have been designed to favour cargo release under specific pH conditions [ 209 ]. Poly(allylamine) phosphate nanocarriers, stable at physiological pH, have been developed to release siRNAs in the cytoplasm after disassembly at low endosomal pH [ 210 ].

Although there have been many successes, some questions remain open and make the clinical translation of the siRNA-based approach very challenging, such as the correct doses to be delivered to patients and the many variabilities observed between individuals and different stages of disease. Further research towards controlled release to reach only specific targets, and the set-up of the best personalised therapy for cancer patients will be necessary in the near future.

Thermal ablation and magnetic hyperthermia

Thermal ablation of tumours includes a series of techniques that exploit heat (hyperthermia) or cold (hypothermia) to destroy neoplastic tissues [ 13 ]. It is known that cell necrosis occurs at temperatures lower than -40°C or higher than 60°C. Long exposures to temperatures between 41°C and 55°C are also effective for tumour cell damage. Moreover, it has been shown that cancer cells are more sensitive to high temperatures than healthy ones [ 211 ].

Hypothermic ablation is due to the formation of ice crystals upon cooling, which destroy cell membranes and finally kill cells. Argon gas is the preferred cooling agent because it can cool down the surrounding tissues to -160°C. Also, gases at their critical point, such as nitrogen, can be exploited since they have a higher heat capacity than argon. However, the technology to control and direct them is not well developed yet [ 10 ].

Hyperthermic ablation currently comprises radiofrequency (RF), microwave and laser ablation [ 10 ].

RF ablation is the most used in clinics, because it is effective and safe [ 212 ]. An alternated current of RF waves is applied to a target zone by an insulated electrode tip, while a second electrode, needed to close the circuit, is placed on the skin surface [ 10 ]. The interaction with the current causes the oscillation of ions in the extracellular fluid, which, in turns, produces heat. The more conductive the medium, the more effective the process. For this reason, RF ablation works very well in the liver and in other areas with a high content of water and ions, whereas it has a poor effect in lungs [ 10 ]. Moreover, the efficiency of the treatment decreases with the size of the lesion, giving the best results for areas not larger than 3 cm 2 [ 213 , 214 ].

Microwave ablation is based on the electromagnetic interaction between microwaves and the polar molecules in tissues, like water, that causes their oscillation and the consequent increase in temperature. Unlike the electrical current in RF ablation, microwaves can propagate through any kind of tissue [ 215 , 216 ], and this allows high temperatures to be reached in a short amount of time, to have a deeper penetration and to treat larger areas of tumours [ 217 ].

Laser therapy exploits the properties of laser beams of being very narrow and extremely focused at a specific wavelength. This makes the treatment very powerful and precise, thus a promising alternative to conventional surgery [ 218 ]. The absorption of the light emitted by the laser results in the heating and subsequent damage of the treated area [ 219 ]. Depending on the specific application, different kinds of lasers can be used. Neodymium:yttrium-aluminium-garnet (Nd:YAG) lasers (wavelength of 1064 nm) and diode lasers (wavelength of 800–900 nm) are used to treat internal organs, since they have a penetration depth up to 10 cm [ 218 ]. Conversely, CO 2 lasers (10,600 nm), with a penetration depth of 10 μm up to 1 mm maximum are used for superficial treatments. Laser therapy is receiving a lot of attention in research because of its advantages compared to other ablation techniques, such as a higher efficacy, safety and precision, and a shorter treatment session needed to achieve the same results [ 220 , 221 ]. Moreover, the fibres to transmit laser light are compatible with MRI, allowing for a precise measure of the temperature and the thermal dose [ 222 ]. However, there are still some limitations to overcome, such as the need of a very skilled operator to place the fibre in the correct position [ 218 ].

Finally, a new way to heat tumour tissues, currently under study, is through magnetic hyperthermia. This technique exploits superparamagnetic or ferromagnetic nanoparticles that can generate heat after stimulation with an alternating magnetic field. The most studied systems in nanomedicine are SPIONs [ 11 ]. The production of heat, in this case, is due to the alignment of magnetic domains in the particles when the magnetic field is applied, and the subsequent relaxation processes (Brownian and/or Neel relaxations) during which heat is released, when the magnetic field is removed and the magnetisation of the particles reverts to zero [ 223 ]. Magnetic hyperthermia can reach any area of the body and SPIONs can also act as MRI contrast agents to follow their correct localisation before the stimulation. The particles can be coated with biocompatible polymers and/or lipid and functionalized with specific ligands to impart targeting properties [ 224 ]. As already mentioned, until now, just a formulation of 15-nm iron oxide nanoparticles coated with aminosilane (Nanotherm) obtained approval for the treatment of glioblastoma [ 31 ]. SPIONs have also been successfully encapsulated in lipid nanocarriers together with a chemotherapeutic agent to combine chemotherapy and hyperthermia [ 49 , 50 ].

Recent innovations in cancer therapy: Radiomics and pathomics

Efficient cancer therapy currently relies on surgery and, in approximately 50% of patients, on radiotherapy, that can be delivered by using an external beam source or by inserting locally a radioactive source (in this case, the approach is named brachytherapy), thus obtaining focused irradiation. Currently, localisation of the beam is facilitated by image-guided radiotherapy (IGRT), where images of the patient are acquired during the treatment allowing the best amount of radiation to be set. Thanks to the introduction of intensity-modulated radiotherapy (IMRT), radiation fields of different intensities can be created, helping to reduce doses received by healthy tissues and thus limiting adverse side effects. Finally, by means of stereotactic ablative radiotherapy (SABR), it has become feasible to convey an ablative dose of radiation only to a small target volume, significantly reducing undesired toxicity [ 225 ].

Unfortunately, radioresistance can arise during treatment, lowering its efficacy. This has been linked to mitochondrial defects; thus, targeting specific functions have proven to be helpful in restoring anti-cancer effects [ 226 ]. A recent study has shown, for example, that radioresistance in an oesophageal adenocarcinoma model is linked to an abnormal structure and size of mitochondria, and the measurement of the energy metabolism in patients has allowed discrimination between treatment resistant and sensitive patients [ 227 ]. Targeting mitochondria with small molecules acting as radiosensitizers is being investigated for gastrointestinal cancer therapy [ 228 ].

Cancer is a complex disease and its successful treatment requires huge efforts in order to merge the plethora of information acquired during diagnostic and therapeutic procedures. The ability to link the data collected from medical images and molecular investigations has allowed an overview to be obtained of the whole tridimensional volume of the tumour by non-invasive imaging techniques. This matches with the main aim of precision medicine, which is to minimise therapy-related side effects, while optimising its efficacy to achieve the best individualised therapy [ 229 ].

Radiomics and pathomics are two promising and innovative fields based on accumulating quantitative image features from radiology and pathology screenings as therapeutic and prognostic indicators of disease outcome [ 12 , 13 , 230 ]. Many artificial intelligence technologies, such as machine learning application, have been introduced to manage and elaborate the massive amount of collected datasets and to accurately predict the treatment efficacy, the clinical outcome and the disease recurrence. Prediction of the treatment response can help in finding an ad hoc adaptation for the best prognosis and outcome. Nowadays, personalised medicine requires an integrated interpretation of the results obtained by multiple diagnostic approaches, and biomedical images are crucial to provide real-time monitoring of disease progression, being strictly correlated to cancer molecular characterisation.

Radiomics is intended as the high throughput quantification of tumour properties obtained from the analysis of medical images [ 14 , 15 , 231 ]. Pathomics, on the other side, relies on generation and characterisation of high-resolution tissue images [ 16 , 232 , 233 ]. Many studies are focusing on the development of new techniques for image analysis in order to extrapolate information by quantification and disease characterisation [ 234 , 235 ]. Flexible databases are required to manage big volumes of data coming from gene expression, histology, 3D tissue reconstruction (MRI) and metabolic features (positron emission tomography, PET) in order to identify disease phenotypes [ 236 , 237 ].

Currently, there is an urgent need to define univocal data acquisition guidelines. Some initiatives to establish standardised procedures and facilitate clinical translation have been already undertaken, such as quantitative imaging network [ 238 ] or the German National Cohort Consortium [ 239 ]. Precise description of the parameters required for image acquisition and for the creation and use of computational and statistical methods are necessary to set robust protocols for the generation of models in radiation therapy. According to the US National Library of Medicine, approximately 50 clinical trials involving radiomics are currently recruiting patients, and a few have already been completed [ 240 ].

Conclusions and future perspectives

In recent years, research into cancer medicine has taken remarkable steps towards more effective, precise and less invasive cancer treatments ( Figure 1 ). While nanomedicine, combined with targeted therapy, helped improving the biodistribution of new or already tested chemotherapeutic agents around the specific tissue to be treated, other strategies, such as gene therapy, siRNAs delivery, immunotherapy and antioxidant molecules, offer new possibilities to cancer patients. On the other hand, thermal ablation and magnetic hyperthermia are promising alternatives to tumour resection. Finally, radiomics and pathomics approaches help the management of big data sets from cancer patients to improve prognosis and outcome.

At the moment, the most frequent entries concerning cancer therapies in the database of clinical trials ( www.clinicaltrials.gov ) involve the terms targeted therapy, immunotherapy and gene therapy, highlighting that these are the most popular methodologies under investigation, especially because, as already mentioned before, they have been shown to be very promising and effective ( Figure 2A ). However, Figure 2B shows that the clinical trials started in the past decade on different therapies mentioned in this review (except for liposomes-based therapies) have increased in number, showing how the interest on these new approaches is quickly growing in order to replace and/or improve conventional therapies. In particular, radiomics, immunotherapy and exosomes are the entries whose number has increased the most in the last 10 years.

The current scenario for cancer research is wide, offering many possibilities for the constant improvement of treatment, considering not only patient recovery but also caring for their well-being during therapy. As summarised in Table 1 , these new approaches offer many advantages compared to conventional therapies. However, some disadvantages still have to be overcome to improve their performances. Much progress has been made, but many others are likely to come in the near future, producing more and more ad hoc personalised therapies.

Conflicts of interest

The authors declare that they have no conflict of interest.

Funding declaration

This work was partially supported by the Fondazione CaRiPLo, grant no. 2018-0156 (Nanotechnological countermeasures against Oxidative stress in muscle cells Exposed to Microgravity—NOEMI) and by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement N°709613, SLaMM).

Authors’ contributions

Carlotta Pucci and Chiara Martinelli contributed equally to this work.

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Perspective

Facing cancer here's when to consider experimental therapies, and when not to.

Jeff Stewart

Experimental therapies for cancer can be tempting when you're sick, but many fail to offer any benefit. Cavan Images/Getty Images/Cavan Images RF hide caption

Experimental therapies for cancer can be tempting when you're sick, but many fail to offer any benefit.

Note: Molecular biologist and author Jeff Stewart has worked more than 15 years as a consultant to drugmakers, scrutinizing data on new treatments to fight cancer. Last July, the 50-year-old father of seven was diagnosed with stomach cancer himself. He spent much of the next 10 months in treatment, while also writing the newly published Living: Inspiration from a Father with Cancer.

His book is a compilation of life lessons and reflections that "helped me endure hard times and avoid harder ones," he says. Framed as a life guide for his kids, it also includes insider advice for anyone facing a cancer diagnosis. The following excerpts have been edited for length and clarity. --Editors

As a cancer patient, I'm getting forwarded many, many articles about early stage cancer treatments and alternative therapies. I think every cancer patient gets these. I'm public about my cancer, so I'm getting these from more than friends and family. I'm getting these also from people I've never met but who are trying to help.

Cancer treatments are not just a personal interest. Part of my job for over 15 years has been to advise pharma companies on cancer drugs. My clients have included big pharma and small biotechs. You'd know the big-pharma names. I've interviewed hundreds of oncologists over the years. Figuring out the scientific and commercial potential of a cancer drug is a normal day on the job for me.

Shots - Health News

Crispr gene-editing may boost cancer immunotherapy, new study finds, how to assess experimental treatments follow the evidence.

Basic rule of cancer treatments: Evidence wins. We need evidence to believe anything works. That's especially true for cancer.

Step one: Is the drug FDA-approved?

Step two: If the drug is approved, is the drug also recommended in cancer guidelines? If the approved drug is not in cancer guidelines, insurance companies aren't going to pay.

Step three: If the drug is neither approved nor in guidelines, is the drug in late-stage clinical trials? That usually means phase III . If so, then maybe a cancer patient can join those. If not in late-stage clinical trials, the drug is too early in testing to help most people who have cancer now.

Amazing result in a test tube? Talk to me in 15 years if I'm still here. Just started phase I clinical trials in people? Still too early to help me. Cures mice? Of all the oncologists I've interviewed about mouse data, I've been told by at least a quarter of them this exact punchline: "I've never treated a mouse for cancer." Yuk, yuk. Funny oncologists. It's not just snark. They have a point buried under their tired joke. Most things that cure cancer in mice don't work in people.

The author signs copies of his new book. Carissa Wadsack-Stewart/Jeff Stewart hide caption

It's worse than you imagine. Nearly every new thing coming out of a university is too early to help anyone who has cancer now. Worse, nearly everything fails. If that sounds jaded, I'm sorry. This is oncologists' lived reality.

Yes, there have been great strides in cancer treatment. The really promising drugs that can do anything in the short term are already in late-stage clinical trials. Oncologists read. They know what's coming. Anything early-stage will not, cannot cure someone who has cancer now. I have to think one of the worst parts of an oncologist's job is to explain why a miracle cure in early development holds no promise at all for a cancer patient today.

Hard truth: Most experimental cancer treatments fail

Here's what most people not immersed in oncology don't get. Even the most promising cancer drugs fail. Cancer drugs have the second-worst failure rate of any disease. Only Alzheimer's is worse.

Think of the tens of millions of dollars spent to get one cancer drug out of a university, into cell lines and mice, and finally into patients to be tested in clinical trials. That's a huge effort. It might take a decade. Those drugs that get tested in people have won a biotech lottery. For any cancer drug to be tested in people, the science has to be amazing . Scientists working on the drug believe it's a lock to work. There may be talk of a Nobel Prize or at least the Lasker Award. Everything seems sure to succeed. What could go wrong?

Do you want to take a guess at how many of those "sure winners" end up passing clinical trials? Seven percent . That's 7% of the best drugs that emerged from the best science and were so promising that a pharma company invested $10 million to more than $1 billion to test the drugs in patients. Ninety-three percent of the "winners" fail.

What about repurposed approved drugs? Approved drugs can be used off label by physicians. What if, say, an anti-parasite drug cured cancer? Why not take that?

The question is, again, where is the evidence? Cancer drugs are special. State laws require insurance companies to pay for cancer drugs any time independent cancer guidelines say the drugs should be used. Even if the drug is not FDA-indicated for the cancer, so long as the evidence shows the drug works, insurance companies must pay. Leading oncologists update cancer guidelines whenever the evidence gets good enough.

Why cancer guidelines are your friend

You see where this is going? For an approved drug not to be on cancer guidelines, the evidence sucks.

This is what I do when I'm forwarded information about nonstandard, alternative, or early cancer therapies: I hit delete. I know, even without reading, the evidence isn't there yet. Things that look fantastic almost always fail. Anything early-stage is not helpful for anyone who has cancer now.

Snake-oil sellers are all over cancer patients . They are all over me. These hucksters will make a buck ripping off cancer patients if they can. These hucksters are vultures (or optimistic to the point of delusion). They don't have evidence. See above.

Even legitimate innovators have a hard time imagining it's possible their cancer drug will fail. But their cancer drug will fail most of the time. It's not something scientists like to admit to themselves.

If you want to take an unproven libido booster, that's one thing. But cancer? Don't waste the time you have left.

What is a cancer patient supposed to do when the standard treatments seem to be pointless? What if the odds with standard treatments are so bad that there might as well be no treatment at all? I'd say to ask your oncologist if there are promising, late-stage clinical trials you can join. This is a perfect question.

A late-stage clinical trial is the best chance a cancer patient has to get a next-generation treatment before approval. We're in a golden age of cancer immunotherapy. There are promising immunotherapies in late-stage clinical trials. If you're enrolled in a trial, not only do you get a chance for a new treatment, you will help move the science along so future patients may benefit.

Understanding the disease and its treatment can ease fears

If you or a loved one has received a cancer diagnosis, I'm sorry. I'm sorry this has happened to you. Cancer is frightening. It's all so complicated that, when we get the diagnosis, we don't know what to think. We barely know what to feel. Understanding cancer and its treatment — even the hard things to hear — helped me be less afraid.

I hope, I pray, my story helps you even though your cancer, your experience, may be different from mine. I'm not going to pretend to be an oncologist and give treatment advice — listen to your oncologist — but if you need to talk, I'm at [email protected] . I'll respond if I'm able.

What's next? "Pre-bunking" instead of debunking bad information about cancer treatment

To my colleagues in the health care industry: There is an opportunity to do good here. The cancer patient needs a trusted, friendly voice to help explain things — on call, 24/7. The health care system isn't prepared to do this. The vacuum is filled now by fraud and fear.

Cancer patients today are not in a neutral information environment. Instead, cancer patients are flooded with false facts and quacks who promise 100% cure rates. That's the reality we live in.

There is one defense against misinformation that we know works: pre-bunking. We must fill cancer patients with facts in forms they can understand before the frauds get to them. How do we do this without hiring a call-center army of oncologists? I'm hopeful that artificial intelligence trained on the best evidence will be a "cancer counselor" that will be there to explain things to patients anytime, day or night.

There is upside for us all: Patients who follow evidence-based medicine have double the chance of surviving their cancer, research has found. Demonstrating an AI cancer counselor has a positive effect on medication compliance or even overall survival in a clinical setting should be possible with a modest number of clinical-trial patients.

The pieces are there. Done right, an AI cancer counselor could save more lives than many cancer treatments. If I survive my cancer, I hope to join you in the effort.

Jeff Stewart is a managing director at Syneos Health Consulting. All views, thoughts and opinions expressed here are his own, and not necessarily those of his employer or others. This essay was adapted from the book, Living: Inspiration from a Father with Cancer, published by Wadsak-Stewart Press on May 15, 2023. He can be reached at [email protected] .

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• experimental cancer treatment
• alternative cancer treatment

Cancer Treatment Research

The Importance of Cancer Treatment Research

Research on the treatment of cancer is fundamental to improving outcomes for all patients affected by the disease. Treatment advances, in combination with innovative diagnostic tools, are leading to therapies that are increasingly tailored to the cancer’s unique traits.

But despite the tremendous progress made in recent decades in treating many types of cancer, effective therapies are still lacking for some cancers, including liver cancer, pancreatic cancer, and certain types of adult and pediatric brain cancer. And even when effective therapies are available, these often stop working as the cancer develops resistance to the treatment.

Also, many people with cancer experience severe side effects of the disease and its treatment. Some of these toxic effects have long-term consequences, including an increased risk of a second cancer . For childhood cancer survivors in particular, the long-term effects of cancer treatment can have a lifelong impact on their quality of life.  

NCI-supported researchers are developing more effective and potentially less toxic treatments, such as targeted therapies, immunotherapies, and cancer vaccines, that are designed to spare healthy tissues more so than systemic treatments. In parallel, researchers continue to improve therapies that have existed for decades, such as chemotherapy, radiation therapy, and surgery. And some studies test whether less intensive therapy, with fewer side effects during and after treatment, can still effectively treat cancer.

Thanks to NCI-funded research, patients with cancer have a greater number of therapeutic options than ever before, many of which are more effective and less toxic than earlier options. But more research is needed to ensure the most effective treatment possible, including better ways to use existing therapies in combination, while maintaining the highest possible quality of life for every individual with cancer.

Selected NCI Activities in Cancer Treatment Research

For more than 50 years, NCI has played an active role in cancer drug development—from conducting preclinical studies in the laboratory to testing potential therapies in humans.

NCI researchers conduct clinical trials to test cancer treatments at the National Institutes of Health in Bethesda, MD, and the institute sponsors trials at cancer centers, hospitals, and community practices around the country. The  Cancer Therapy Evaluation Program (CTEP) functions as the institute’s primary clinical evaluator of new anticancer agents, radiation treatments, and surgical methods.

While many companies and institutions around the world conduct research on cancer treatments, NCI meets needs that industry does not. These include developing and testing treatments for rare cancers and conducting trials to test the safety and effectiveness of using less treatment or no treatment at all.

Examples of NCI-supported activities in treatment research include:

Discovering New Cancer Drugs

NCI Treatment Research and the National Cancer Plan

NCI supports a broad variety of research that aligns with the National Cancer Plan’s goal to develop effective treatments. Read about the plan and this goal.

• NCI’s  Developmental Therapeutics Program (DTP) provides free services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new anticancer agents, including targeted therapies that work through cancer’s unique genetic alterations. DTP supports all stages along the critical path of preclinical drug discovery and development, from high-throughput tumor cell–based screening to first-in-human clinical trials.
• The NCI-60 Human Tumor Cell Lines Screen , which includes 60 human tumor cell lines representing nine different types of cancer, is a free resource available to the research community worldwide to evaluate compounds for anticancer activity. The NCI-60 screen tests up to 7,000 compounds yearly and prioritizes compounds with promising anticancer potential for further evaluation.
• The Comparative Oncology Program is a unique program that helps researchers improve the assessment of novel therapies for humans by treating pet animals with naturally occurring cancers. The program gives these animals the benefit of cutting-edge research and therapy, and it provides researchers a better understanding of cancer biology and cancer's response to treatment.

Understanding Treatment Response

• The Acquired Resistance to Therapy Network (ARTNet) uses team science to study the mechanisms of acquired resistance to cancer therapies and disease recurrence. This program replaces and builds on progress made by the  Drug Resistance and Sensitivity Network (DRSN) , an NCI and Cancer Moonshot–created program to explore why some cancer cells are innately sensitive to treatment and to identify strategies for circumventing drug resistance in tumors.
• NCI contributes to the international  Human Cancer Models Initiative , which generates novel human tumor-derived culture models with the goal of creating cancer models that replicate patients’ tumors as faithfully as possible. The models are annotated with genomic and clinical data and are available to the wider research community to define cancer pathways, determine mechanisms of drug resistance, and assess responses to small molecules.

Improving Current Cancer Treatments

NCI Fiscal Year 2025 Professional Judgment Budget Proposal

Each year, NCI prepares a professional judgment budget to lead progress against cancer.

• NCI’s first-of-its kind precision medicine trial called Molecular Analysis for Therapy Choice (NCI-MATCH) tested the effectiveness of treating tumors in adults and children based on matching targeted therapies to specific genetic alterations in the tumors, regardless of tumor type. Using information learned from NCI-MATCH, three more precision medicine trials—called ComboMATCH, MyeloMATCH, and iMATCH —will test whether drug combinations can overcome resistance to treatment, evaluate new treatments for myeloid leukemia and myelodysplastic syndrome, and examine immune profiles and tumor markers for responsiveness to immunotherapy, respectively.
• NCI’s  Radiation Research Program (RRP) provides expertise to investigators who perform radiotherapy studies and helps direct radiation research. Methods that more precisely target radiation therapy to tumors while sparing as much normal tissue as possible are critical for maintaining patients’ quality of life and improving cure rates.
• Immunotherapy is a type of cancer treatment that helps cells in a patient’s own immune system detect and eliminate cancer, including some difficult-to-treat tumors. Researchers are working collaboratively through the Immuno-Oncology Translational Network (IOTN) and the Pediatric Immunotherapy Network (PIN) to speed up the development of new immunotherapies to treat and prevent adult and pediatric cancers.
• NCI brings together researchers from across the institute and the National Institutes of Health to work on cancer immunology and immunotherapy research to discover, develop, and deliver immunotherapy approaches that can prevent and treat cancer and cancer-associated viral diseases. This work has pioneered important research on the basic mechanisms of immune response, including how immune system cells and cancer cells interact, and on the development of better vaccines and immunotherapies.

Moving Discoveries into the Clinic

• The  Translational Research Program (TRP) supports efforts through the Specialized Programs of Excellence (SPOREs) to translate novel scientific discoveries from the laboratory to the clinic for testing in humans. This work includes determining the biological basis for observations made in cancer patients or in populations at risk for cancer.
• The  NCI Experimental Therapeutics Program (NExT)  focuses on advancing discoveries in basic and clinical research into new therapies to treat cancer patients. This translational research effort unites the drug development expertise of multiple NCI research programs and the facilities at the NIH Clinical Center to advance new therapeutic interventions from both the private and public sectors.

Supportive Care, Symptom Management, and the National Cancer Plan

NCI supports research on supportive care and symptom management to improve the lives of people living with cancer. This research aligns with the National Cancer Plan’s goal to deliver optimal care. Read about the plan and this goal.

Supportive Care and Symptom Management

• The Supportive Care and Symptom Management program focuses on the prevention and treatment of acute and chronic symptoms and side effects related to cancer and its treatment, such as fatigue, musculoskeletal pain, nerve damage, and fertility issues. Researchers also study the effect of treatment on cancer patients' quality of life and the psychosocial issues and strategies for care at the end of life.
• NCI has established a collaborative research consortium, called  Improving the Management of Symptoms during and following Cancer Treatment (IMPACT) , to determine the best approaches for symptom management in cancer care delivery. Research centers within this consortium are testing integrated symptom monitoring and management systems in the clinic and analyzing the effects of those systems on patient outcomes, cancer treatment delivery, and health care utilization using randomized designs.

Recent Research Findings in Cancer Treatment

• For Kids with Medulloblastoma, Trial Suggests Radiation Can Be Tailored
• Revumenib Shows Promise in Treating Advanced Acute Myeloid Leukemia
• Dexrazoxane Protects the Heart Long Term for Kids Being Treated for Cancer
• Enhertu Marks First Targeted Therapy for HER2-Mutant Lung Cancer
• NCI Study Finds that Immunotherapy Substantially Increases Survival of People with Lymphomatoid Granulomatosis
• Disguising Cancer as an Infection Helps the Immune System Eliminate Tumors
• NCI clinical trial leads to atezolizumab approval for advanced alveolar soft part sarcoma
• New T-cell therapy shrinks solid tumors in early-phase clinical trial
• FDA Approves BCMA-Targeted CAR T-Cell Therapy for Multiple Myeloma