Pancreatic cancer: the solution sought in “survivors” like Judge Ruth Ginsburg, who died 11 years after diagnosis

Pancreatic cancer offers few positive outcomes. According to data from the American Cancer Society conference on the subject, only 9% of people with pancreatic cancer are still alive five years after diagnosis. However, the key would surely be found in care and screening earlier than those currently carried out. By removing the initial tumor at an extremely early stage, it would therefore be possible to extend the duration of patients. Like Ruth Bader Ginsburg, the judge at the Supreme Court of the United States, who had been operated on for pancreatic cancer in 2009 and who died in September 2020, 11 years later.

Diagnose before metastasis

But understanding how to lengthen the life of people suffering from pancreatic cancer is essential, as medicine seems to be lagging behind in this area. By relying on the journey of survivors, like Ruth Ginsburg, the researchers believe they can complete their knowledge. “One of the factors most strongly correlated with 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 the 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, rising from 6% in 2012 to 9% currently. This gap is explained by the violence of the disease; pancreatic cancer is most often fatal, because of its ability to become metastatic quickly. Moreover, when a diagnosis of pancreatic cancer is made, it is generally late, and metastasis is already underway.

“Our patients quickly fall ill, 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 since the emergence of new chemotherapies in 2011 and 2013 has improved the life expectancy of patients with metastatic pancreatic cancer. As Kim Reiss, associate director of the hematology and oncology fellowship program at Penn Medicine, points out:

“We have significantly improved prognosis with the multi-agent chemotherapy combinations we have used.”

Jennifer Knox, co-director of the McCain Center for Pancreatic Cancer, agrees: “Patients may only have one chance to receive chemotherapy, and we also need many more options and better options for them. What we really want is a biomarker of the patient’s tumor that would predict which diet would do better than average in order to pick that one, but that’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. In particular, researchers can rely on the “Know Your Tumor” program, a large clinical trial which showed that a quarter of 1,100 patients with pancreatic cancer had tumors with genetic variants that could be associated with targeted therapies. According to the researchers, this concordance between chemotherapy and the genetic variations specific to each patient could make it possible to improve the survival of patients by one year. This advice was followed by the American Society of Clinical Oncology, which last August updated its guideline to recommend germline and tumor genomic testing for patients with pancreatic cancer.

Betting on T cells

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

“Cold tumors often have defects in pathways that help immune cells recognize tumor cells. But long-term pancreatic cancer survivors don’t have these flaws.”, sums up Vinod Balachandran. By exploring the subject further with his teams, the researcher realized that the tumors of survivors are enriched in innate lymphoid cells 2 (ILC2) which do not need antigens to trigger the immune response. Coupled with the cytokine interleukin 33 (IL-33), it stimulates the production of T lymphocytes, which stimulates the immune system and increases 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 use this information to develop the next wave of therapy for patients.”, concludes the researcher.