RAS is an oncogene, which is a gene that when mutated causes cancer. RAS (which is a family of genes including KRAS, HRAS, and NRAS) is commonly mutated in cancer. RAS mutations, usually in the KRAS protein, occur in about one in four cases of lung cancer.
These gene mutations are found only in the cancer cells and cause the RAS proteins, which act a bit like a 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 Alice Shaw, MD, PhD, chief of Strategic Partnerships and co-director of the Center for RAS Therapeutics, started studying the RAS oncogene at the beginning of her career as a medical oncologist and physician-scientist. Her research focused on how RAS mutations drive cancer, and how to selectively target RAS mutant cancers. Over a decade later, as head of translational clinical oncology at Novartis, Shaw oversaw the clinical development of a new KRAS inhibitor.
Shaw’s focus now is on bringing RAS experts together in one center to advance treatments for patients with RAS-mutated lung cancer.
“The landscape of RAS therapeutics is highly complex and dynamic,” says Shaw. “It’s such an exciting time, but it can also feel overwhelming. The Center for RAS Therapeutics is going to be incredibly valuable in helping us evaluate emerging new therapies in order to select the most promising ones for patients with RAS-mutated lung cancer.”
Are there treatments for RAS-mutated lung cancer?
Currently there are two RAS inhibitors approved by the U.S. Food and Drug Administration for the treatment of RAS-mutated non-small cell lung cancer. Those inhibitors target a specific RAS mutation called KRAS G12C.
Prior to approval of these therapies, patients with RAS driven non-small cell lung cancers had no targeted therapy options and could only be treated with chemotherapy or immunotherapy. However, only about 35% of people taking these RAS inhibitors respond to the drugs, and those responses only last about six months.
“The first KRAS G12C inhibitors were really groundbreaking, but their efficacy has been somewhat limited,” says Shaw. “To have a truly transformative impact on outcomes, we’re almost certainly going to need to develop more potent next-generation RAS inhibitors as well as combination therapies that can induce deeper and more durable responses.”
What research is going on for RAS-mutated lung cancer?
The Center for RAS Therapeutics will advance novel treatment approaches for patients with RAS-driven cancers. In lung cancer, investigators are focusing on evaluating emerging RAS inhibitors to determine which have the most promise in early-phase clinical trials.
The team will also focus on research that reveals more about how RAS-mutated cancers evade RAS inhibition to inform the design of clinical trials testing promising combination therapies for the treatment of RAS-mutant disease.
“Within the last decade, there has been a surge of interest in RAS inhibition now that we have our first approvals in KRAS G12C mutant lung cancers. Drug development has advanced and is coming up with clever approaches to designing small molecule drugs and other types of therapeutics, like degraders, antibody-drug conjugates, and immune-based strategies,” says Jia Luo, MD, a Dana-Farber clinical investigator who has led several clinical investigations focused on RAS-mutated lung cancer. “There’s a lot of promise.”
Learn more about the clinical trials and clinical research related to RAS-mutated lung cancer.