the solution sought among the “survivors” such as judge Ruth Ginsburg, who died 11 years after the diagnosis



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THE ESSENTIAL

  • Pancreatic cancer offers little chance of long-term survival. However, it is possible to extend the time by a few years.
  • Early management can improve the chances of survival.
  • Chemotherapy, immunotherapy, and treatments to strengthen T lymphocytes are good alternatives to gain a few years of life.

Pancreatic cancer doesn’t offer many positive results. According to data from the American Cancer Society conference on the subject, only 9 percent of people with pancreatic cancer are still alive five years after diagnosis. However, the key would surely be found in treatment and screening ahead of those currently being carried out. By removing the initial tumor at an extremely early stage, it would therefore be possible to extend the life span of patients. Like Ruth Bader Ginsburg, a US Supreme Court Justice, who had been operated on for pancreatic cancer in 2009 and passed away in September 2020, 11 years later.

Diagnosis before metastases

But understanding how to extend the lives of people with pancreatic cancer is essential, as medicine seems to be lagging behind in this area. By tapping into the journey of survivors, such as Ruth Ginsburg, the researchers believe they will be able to integrate their knowledge. “One of the factors most related to long-term survivors was the density of CD8 T cells in their tumors, suggesting that these survivors may provide clues as to how to activate immunity.“, Analyzes Vinod Balachandran, surgeon at Memorial Sloan Kettering Cancer Center (United States).

While five-year survival rates for some cancers have increased dramatically over the past few decades, improvements for those with pancreatic cancer have been more limited, from 6 percent in 2012 to 9 percent today. This difference is explained by the violence of the disease; pancreatic cancer is often fatal, due to its ability to rapidly metastasize. Also, when a diagnosis of pancreatic cancer is made, it is usually late and metastases have already begun.

Our patients get sick quickly, they are fragile, it is difficult to help them, says David Tuveson, president of the American Association for Cancer Research. The combination of rapid progression and deconditioning can also make it difficult to enroll patients in clinical trials. “

The Rise of Next Generation Chemotherapy

Despite everything, hope remains as the emergence of new chemotherapies in 2011 and 2013 has improved the life expectancy of patients with metastatic pancreatic cancer. As Kim Reiss, deputy director of the Hematology and Oncology Scholarship Program at Penn Medicine, points out:

We have greatly improved the prognosis thanks to the multi-agent chemotherapy combinations we used. “

Jennifer Knox, co-director of the McCain Center for Pancreatic Cancer, agrees: “Patients may only have one chance of getting chemotherapy and we also need a lot more and better options for them. What we really want is a patient tumor biomarker that predicts which diet would do better than average to choose which one, but it’s not easy to find.. “

Research is currently underway to match patients with metastatic pancreatic cancer with the chemotherapy regimen most likely to be effective based on genetics or other biomarkers. Specifically, researchers can draw on the Know Your Tumor program, a large clinical study that showed that a quarter of 1,100 pancreatic cancer patients had cancers with genetic variants that could be associated with targeted therapies. According to the researchers, this concordance between chemotherapy and each patient’s specific genetic variations could improve patient survival for one year. This advice was followed by the American Society of Clinical Oncology, which last August updated its guidelines to recommend germline and tumor genomic testing for patients with pancreatic cancer.

Focus on T lymphocytes.

Some pancreatic cancer patients have higher levels of certain T cells and tend to live longer, which is odd given the increase in cancer immunotherapies that use the same process to kill tumors. Normally, immunotherapy is effective in 20% of cancers, especially those described as “hot”. In 80% cold tumor, the efficacy of immunotherapy is mixed. However, most pancreatic cancers are cold tumors.

Cold tumors often have defects in the pathways that help immune cells recognize cancer cells. But long-term pancreatic cancer survivors don’t have these defects“Summarizes Vinod Balachandran. Exploring the topic in depth with his teams, the researcher noted that the survivors’ tumors are enriched in innate lymphoid 2 cells (ILC2) that do not need antigens to trigger the immune response. cytokine interleukin 33 (IL-33) stimulates the production of T cells, which stimulate the immune system and increase survival Vinod Balachandran is currently developing a drug that works on this principle.

It is very important for the pancreatic cancer research community to understand how the immune system interacts with pancreatic cancer and then to use this information to model the next wave of therapy for patients.“, Concludes the researcher.



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