Pancreatic cancer has long been difficult to detect and treat. Dana-Farber experts in the Hale Family Center for Pancreatic Cancer Research, however, are working to change that with research efforts in three key areas that are poised to advance early detection, early intervention, and treatment of the disease.
They presented these topics for discussion with other researchers at the American Association of Cancer Research (AACR) special conference on Advances in Pancreatic Cancer Research in October 2025.
A pancreatic cancer cell.
Research into early detection of pancreatic cancer
Approximately 80% of patients with pancreatic cancer discover the disease late, when it has already spread and cannot be surgically removed. Currently, there is no recommended screening test for pancreatic cancer, though patients who are at a high risk, such as those with an inherited risk of pancreatic cancer, may be recommended for screening using imaging tests.
Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber, and colleagues are pursuing research at Dana-Farber that could lead to new ways to detect pancreatic cancer earlier.
- Using artificial intelligence (AI) to detect warning signs of pancreatic cancer. Wolpin and colleagues are exploring whether AI algorithms can pick up patterns in medical records, such as unexplained weight loss, diabetes, or changes in imaging scans, that could indicate the development of pancreas cancer in a patient. If so, these algorithms could be used to direct people for screening.
- Early identification of small pancreatic cancers. Lesions on the pancreas appear long before cancer develops, but they are too small to pick up using existing imaging tools. In fact, just about every adult has pre-invasive lesions in their pancreas and most don’t become cancerous. Dana-Farber investigators Matthew Yurgelun, MD, and Michael Rosenthal, MD, PhD, are leading a clinical trial for patients with a high risk of pancreatic cancer to study new ways to detect pancreatic cancer early, before it has spread beyond the pancreas, using imaging and blood-based biomarkers.
“If we’re going to improve the lives of patients with this cancer, earlier detection has to be part of that,” says Wolpin.
Research into the effectiveness of RAS therapeutics for pancreatic cancer
The introduction of medicines that target a family of genes called RAS represent a huge leap in potential treatment for patients with pancreatic cancer. RAS therapeutics are designed to inhibit or degrade mutant RAS proteins and slow the growth of cancer. Currently, dozens of RAS therapeutics are being tested in clinical trials for a range of cancers.
Approximately 95% of all pancreatic cancers harbor RAS mutations. No RAS-targeted therapies are approved for the treatment of pancreatic cancer yet, but clinical trials are underway:
- Based on encouraging results from a phase 1 clinical trial, Wolpin and other investigators are leading a phase 3 study of a RAS inhibitor called daraxonrasib in patients with metastatic pancreatic cancer who have progressed after receiving first line chemotherapy. Current standard of care is a second line of chemotherapy, which is has limited effectiveness. But in the phase 1 trial, approximately 90% of patients who received daraxonrasib had some benefit from the medicine. The hope is that the trial will demonstrate a RAS inhibitor to be more effective than current chemotherapy in treating pancreatic cancer.
- Trials of several other promising RAS-targeting therapies are also underway at Dana-Farber.
If approved, RAS therapeutics could provide a foundation for building even more effective and durable combination therapies for pancreatic cancer. RAS therapeutics might also be appropriate for the treatment of early-stage RAS-mutant pancreatic cancer or even for the interception of pre-cancerous lesions with RAS mutations, which will become increasingly important as early detection and screening approaches improve.
“The revolution in targeting RAS has been one of the biggest therapeutic advances in the history of clinical care for pancreatic cancer patients,” says Andrew Aguirre, MD, PhD, co-director of the Center for RAS Therapeutics and Associate Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber. “We believe we are on the cusp of an amazing new era in pancreatic cancer treatment in the next few years if these new RAS inhibitors continue to prove safe and effective in the clinic.”
Research to develop novel immunotherapies for pancreatic cancer
A key to the treatment of cancer is combination therapies that help stave off resistance to targeted therapies. In other cancers, combinations that include immunotherapy have been successful, but pancreatic cancers tend not to respond to immunotherapies.
However, new research by William Freed-Pastor, MD, PhD, a physician-scientist in the Dana-Farber Center for Gastrointestinal Oncology and Hale Family Center for Pancreatic Cancer Research at Dana-Farber, is opening the door to the development of immunotherapies specifically for pancreatic cancers. His work has uncovered new flags on the surface of cells called antigens that are prominent in pancreatic cancer but not on other cells. These flags may be recognized by the immune system and could make good targets for new immunotherapies.
Efforts are underway to explore the possibility of developing novel immunotherapies, including cancer vaccines and T cell therapies.