RAS is an oncogene, which is a gene that when mutated causes cancer. RAS (consisting of a family of genes including KRAS, HRAS, and NRAS) is commonly mutated in cancer. Approximately 92 percent of pancreatic cancers have a KRAS mutation.
These gene mutations are found only in the cancer cells and cause the RAS protein, which acts a bit like traffic lights, to be stuck on green much longer than in normal cells. The result is a nearly never-ending flow of growth signals into the cell. Those signals cause the cell to become cancerous.
Dana-Farber’s Andrew Aguirre, MD, PhD, a medical oncologist and physician scientist, associate director of the Hale Family Center for Pancreatic Cancer Research, and co-director of the Center for RAS Therapeutics at Dana-Farber, leads a research laboratory that studies pancreatic cancer biology and RAS signaling. His group has published several seminal investigations on resistance to RAS inhibitors.
Aguirre’s focus now is on bringing RAS experts together in one center to advance treatments for patients with RAS-mutated pancreatic cancer.
“RAS-targeting therapies hold tremendous promise, but we have not yet hit a home run. More research is required to understand how best to use RAS-inhibitors to help patients,” says Aguirre. “Collaboration within Dana-Farber and beyond will be critical to ensure that these new treatments have the greatest impact for patients.”
Are there treatments for RAS-mutated pancreatic cancer?
There currently are no approved RAS-targeted medicines for pancreatic cancer, but several have been tested in clinical trials or have plans to be tested.
Early clinical trials of RAS inhibitors have shown encouraging results in patients with pancreatic cancer who have a KRAS mutation, However, the cancers are still able to find a way to evade the therapy, leading to relapse. Aguirre’s research recently revealed how pancreatic cancer cells changed to evade RAS inhibitors. They do so by morphing into cells that no longer rely on RAS to grow.
Aguirre’s findings point to a novel approach to treating pancreatic cancer that involves a combination of chemotherapy and a RAS inhibitor. The hope is that the two treatments together might target all cancer cells, not just those driven by RAS.
“This early data suggesting that these RAS inhibitors are working in patients with advanced disease whose cancer has progressed after receiving chemotherapy gives us a strong rationale for combining the two,” says Brandon Huffman, MD, a Dana-Farber medical oncologist who leads KRAS inhibitor clinical trials in gastrointestinal cancers. “We are hoping we see a synergistic combined effect that helps patients live longer and better.”
What research is going on for RAS-mutated pancreatic cancer?
A multitude of RAS inhibitors are becoming available, providing researchers with new tools and possibilities for the treatment of pancreatic cancer. At Dana-Farber, the Center for RAS Therapeutics, along with the Hale Family Center for Pancreatic Cancer Research, will provide centralized expertise regarding RAS-targeted treatment and will offer clinical trials of RAS therapeutics for pancreatic cancer patients. Dana-Farber investigators will work collaboratively to match patients with pancreatic cancer to appropriate clinical trials.
The center will also perform basic science to learn more about RAS in cancer, and it will apply those discoveries to inform new possible ways to approach treatment of RAS-mutant disease.
Learn more about the clinical trials and clinical research related to RAS-mutated pancreatic cancer.