Immunotherapy for pancreatic cancer is currently in clinical trials, providing potential new options for patients with this difficult-to-treat cancer.
The pancreas is an organ of the digestive system located behind the stomach, bordering the spleen and small intestine. It has two primary functions: an endocrine function that releases insulin and glucagon into the bloodstream, and an exocrine function that produces digestive enzymes that are released into the small intestine.
The incidence of pancreatic cancer is rising, and some reports project that the number of new pancreatic cancer cases and pancreatic cancer deaths will more than double by 2030. Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases.
Pancreatic cancer is very difficult to detect or to diagnose at early stages of disease. It often develops without early symptoms, there is no widely used method for early detection, and although some risk factors have been identified (such as tobacco use, family history of pancreatic cancer, and a personal history of pancreatitis, diabetes, or obesity), few patients diagnosed with pancreatic cancer have identifiable risk factors.
Pancreatic cancer is one of the world's most lethal cancers, and the fourth-leading cause of cancer-related death in the United States. Each year, an estimated 460,000 people globally—and 60,000 in the U.S.—are diagnosed with pancreatic cancer, and it causes approximately 430,000 deaths worldwide and 48,000 in the U.S.
Pancreatic ductal adenocarcinoma (PDA) is highly lethal; for all stages combined, the 1- and 5-year relative survival rates are 27% and 9%, respectively, making it the only cancer with an overall 5-year survival rate in the single digits.
There are currently limited effective treatments for patients with advanced disease who are ineligible for surgery, a prognosis representing the majority of pancreatic cancer diagnoses. Pancreatic cancer is significantly more resistant to chemotherapy in comparison to other cancer types, leaving patients with fewer options when it comes to treating the disease in its earlier stages.
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Traditional treatments for pancreatic cancer include: surgical resection, radiation, ablative treatments, and chemotherapy.
Currently, the only treatment for pancreatic cancer that has any chance of curing the patient of the disease is complete surgical removal of the pancreas, a procedure for which fewer than 20% of those diagnosed are eligible. Many patients who do proceed with surgery will ultimately relapse, pointing to the urgent need for more effective treatments that are more likely to prevent eventual relapse.
Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently two FDA-approved immunotherapy options for a small subset of patients with pancreatic cancer, and many more are being investigated in clinical trials.
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced pancreatic cancer that has DNA mismatch repair deficiency (dMMR)
- Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced pancreatic cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)
Due to its consistently poor outlook and the current lack of effective treatment options, pancreatic cancer patients are highly encouraged to seek clinical trials in all cases.
Find a Pancreatic Cancer Clinical Trial
At the Cancer Research Institute, we are dedicated to improving the quality of life and prognostic landscape for patients diagnosed with this destructive disease. With the aid of our donor network, we continue to provide funding to leading scientists working in the field of pancreatic cancer research and treatment.
CRI discoveries and ongoing work in pancreatic cancer research and treatment include:
- A study by former CRI predoctoral fellow Eric Lutz, Ph.D., and CRI’s Scientific Advisory Council member and clinical trial researcher Elizabeth Jaffee, M.D., found that a vaccine called GVAX could make a “non-immunogenic” pancreatic tumor more likely to be detected by the immune system.
- In 2012, Lauren Bayne, Ph.D., a former CRI predoctoral fellow at the University of Pennsylvania, and Yuliya Pylayeva-Gupta, Ph.D., a 2009-2012 CRI postdoctoral fellow at NYU Langone Medical Center, independently showed that the mutation in the KRAS gene—which is mutated in nearly all pancreatic cancers—triggers expression of the immune stimulating molecule GM-CSF, which recruits immature immune cells that can suppress the anti-tumor activity of other immune cells.
- CRI-funded graduate student Albert Lo validated FAP+ stromal cells as candidate targets for pancreatic cancer immunotherapy through preclinical studies of adoptive therapy with CAR T cells modified to target FAP.
- CRI postdoctoral fellow Ingunn M. Stromnes, Ph.D., developed a mouse model of pancreatic ductal adenocarcinoma, discovered that the tumors were attracting Gr-MDSCs (a type of regulatory immune cell) by releasing GM-CSF (a protein), and administered a monoclonal antibody targeted against a particular antigen found on Gr-MDSCs, which allowed killer T cells to enter the tumors and launch an assault.
- Robert Vonderheide, M.D., D.Phil., a member of CRI’s Scientific Advisory Council, is leading a CRI clinical trial that is targeting the CD40 pathway in combination with chemotherapy and checkpoint immunotherapy in patients with metastatic pancreatic cancer. Early results have demonstrated the promise of this approach.
See what pancreatic cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way cancer is treated—curing more people and saving more lives.
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