UC San Francisco researchers took on one of science’s lost causes. Today, their work has finally ushered in hope for pancreatic cancer — one of medicine’s most devastating diseases.
The Food and Drug Administration (FDA) recently approved daraxonrasib, the first drug shown to substantially extend life expectancy for pancreatic cancer patients. In clinical trials, including at UCSF, the once-daily medication doubled life expectancy to a median of more than 13 months in patients with metastatic pancreatic cancer whose cancer had progressed on standard chemotherapy compared with less than seven months for those who continued to receive standard chemotherapy.
Marketed as Rasonque, the drug targets a protein called RAS. RAS mutations are found in about 20% of all cancers. For more than three decades, scientists believed these mutations were impervious to treatment. In 2013, Professor of Cellular and Molecular Pharmacology Kevan Shokat, PhD, used technology developed by Pharmaceutical Chemistry Professor Jim Wells, PhD, to discover a tiny “pocket” on the surface of the mutated RAS protein that proved to be its Achilles’ heel. Shokat’s lab developed drugs that could snuggle into the pocket and bind to the protein, weakening and killing the cancerous cells.
Professor of Medicine Andrew Ko, MD, is a pancreatic cancer specialist at UCSF Health and led the daraxonrasib clinical trial at UCSF in partnership with Revolution Medicines, which Shokat co-founded.
Ko tells us what to know about the headline-grabbing drug and what’s next for pancreatic cancer.
This is a targeted therapy that blocks KRAS signaling in cancer cells. Mutations in the RAS family of genes, and more specifically in KRAS, occur in upwards of 90% of pancreatic cancers. KRAS normally acts like an on-off switch for cell growth, but mutations can cause it to get stuck in the “on” position, signaling cancer cells to keep growing.