On April 13, 2024, the Hirshberg Foundation held the 18th Annual Symposium on Pancreatic Cancer. It was an honor to welcome Scientific Advisory Board member, Dr. Eileen O’Reilly to share a progress report on the state of pancreatic cancer research. Dr. O’Reilly is a professor of medicine at the Weill Cornell College of Medicine, a medical oncologist at Memorial Sloan Kettering Cancer Center, a principal investigator of multiple phase one, two, and three clinical trials for pancreatic cancer, and an international leader in finding ways to better treat this disease.
Dr. O’Reilly provides an overview of pancreatic ductal adenocarcinoma (PDAC), the current treatment landscape, and the shifting epidemiology of the disease. She focuses on the current and evolving treatments for advanced-stage pancreas cancer, DNA-damage-directed therapies, KRAS-directed therapies, and new emerging approaches.
A decade ago, the primary form of treatment for pancreatic cancer was limited to chemotherapy based on our understanding of the disease. Now, pancreas cancer is approached as a KRAS-altered disease, which provides a few more avenues for treatment. The current standard therapy includes three main chemotherapy options: mFOLFIRINOX, Gemcitabine with nab-paclitaxel, and NALIRIFOX. There is also emerging evidence for more use of maintenance therapy or a de-escalated chemotherapy. For certain patients, there is also the option for integration of local therapies such as radiation, surgery, or ablation.
One main area of research for pancreas cancer treatment is KRAS, as about 88 to 90% of people with pancreas cancer will have an alteration in KRAS. KRAS, an important signaling pathway in pancreas cancer, is involved in the growth and metastatic potential of this disease, and it comes in various flavors. Most common in pancreas cancer is something called KRAS G12D, followed by G12V, followed by G12R. One KRAS alteration to highlight is G12C because current regulatory approvals and drugs are available for use in the clinic to treat the small subset of individuals with this specific mutation. Targeting KRAS directly or indirectly, tackling the protein, working on the gene itself, looking to different versions of the gene, and combining it with other things are avenues of current investigation for pancreatic cancer.
Genetic targeting, in terms of BRCA1, BRCA2, and PALB2, is another important topic for pancreatic cancer treatment. Although these cases comprise 5 to 8% of this disease, they’re a very important subset that can benefit from specific treatments. These treatment options include platinum-based therapy and PARP inhibitors. Genetic targeting also influences future treatment directions, and some very interesting areas are being studied.
A great deal is happening around the globe to advance research and treatment options for pancreatic cancer. As Dr. O’Reilly said, “you’ll see that there’s real progress happening and we’re just on the cusp of I think very important developments in this disease that hopefully will translate into improvements and outcomes for people.” We thank Dr. O’Reilly for her presentation and look forward to sharing more as these treatment options develop.