In a Salt Lake City laboratory, scientists are zeroing in on a stubborn enemy — a deadly skin cancer that has long lacked a targeted treatment. Researchers at Huntsman Cancer Institute at the University of Utah say a new drug called daraxonrasib could finally fill that gap for patients with NRAS-driven melanoma, an aggressive form of the disease.
The drug, developed by Revolution Medicines, works by targeting and switching off RAS proteins that drive cancer growth when they mutate. About a quarter of all melanoma cases — the deadliest form of skin cancer — are caused by NRAS mutations, a subtype of RAS.
"The remarkable success of daraxonrasib in the treatment of pancreatic cancer indicates that we are in an era where even the most recalcitrant RAS-driven cancers can be treated," said Martin McMahon, Ph.D., senior director of preclinical translation at Huntsman Cancer Institute and a professor of dermatology.
The research team, led by McMahon and Mona Foth, Ph.D., tested the drug in preclinical models, including actual tumor samples from melanoma patients. Their findings, published in the journal Cancer Research, showed that every NRAS-driven model responded to treatment — a result the scientists found striking.
"All our NRAS-driven models were very responsive to this RAS inhibitor," Foth said. "It's actually quite rare that we see shrinkage of NRAS-driven tumors. It's inspiring to think that these results could potentially lead to a new patient therapy that will help them overcome their disease."
Today, most melanoma patients start with immunotherapy, which uses the body's own immune system to fight cancer. It works well for roughly half of patients. But when immunotherapy stops working or stops being an option, patients with other genetic mutations like BRAF have approved targeted therapies to fall back on. Patients with NRAS-driven melanoma have had nothing.
"Patients with other mutations like BRAF have access to clinically approved second-line treatments," McMahon said. "But patients with NRAS-driven melanoma do not have effective targeted therapies to treat their cancer."
Researchers did observe that some models developed resistance to daraxonrasib, which researchers tied to specific genetic changes. They say more work is needed to find drug combinations that could overcome resistance and deepen responses.
The team hopes daraxonrasib will move into a clinical trial for patients who either can't receive immunotherapy or whose immunotherapy has failed. Neli Ulrich, Ph.D., executive director of Huntsman Cancer Institute, called the work an example of how lab discoveries and clinical research can come together to create new options for patients.
"We are proud to contribute to advances that have the potential to change treatment options for our patients with melanoma," Ulrich said.