RRAS 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 95 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,” 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 the first RAS inhibitor to be evaluated in a large, randomized phase 3 trial showed a substantial prolongation of survival for patients with previously treated metastatic pancreatic cancer compared with chemotherapy. The drug, called daraxonrasib, has been given an initial regulatory green light for expanded access in previously treated metastatic pancreatic cancer.
Trials of several other promising RAS-targeting therapies are also underway at Dana-Farber. Learn more about RAS inhibitors for pancreatic cancer.
Investigators are building on this success with another novel approach to treating newly diagnosed metastatic pancreatic cancer. An ongoing clinical trial, RASolute 303, is comparing current standard of care —chemotherapy — to daraxonrasib alone or a combination of the two as a first-line treatment for patients with metastatic pancreatic cancer.
“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 research advances in pancreatic cancer.
Learn more about the clinical trials and clinical research related to RAS-mutated pancreatic cancer.