How Will Successfully Targeting KRAS Change Pancreatic Cancer Treatment?

In this episode of Oncology On the Go, CancerNetwork® spoke with Frank McCormick, PhD, about the arc of KRAS-targeted drug development over his 40-year career. He explained why KRAS was long considered “undruggable.” He walked through the origins of the National Cancer Institute’s RAS Initiative, which he helped lead starting in 2013, and how that effort produced several of the drugs now advancing through clinical trials for pancreatic cancer.

A central moment of the conversation centers on the phase 3 RASolute-302 trial (NCT06625320) data, which showed that daraxonrasib nearly doubled overall survival compared with standard of care in pancreatic cancer. McCormick described this as a turning point that transformed pancreatic cancer from a historically difficult indication into one now seeing a wave of new drug development.

McCormick also discussed his vision for cancer prevention. He described a roughly 20-year window between initiating KRAS mutations and clinical disease, and outlined a future in which a safe, well-tolerated KRAS inhibitor could be taken periodically to eliminate precancerous lesions before they progress, potentially preventing KRAS-driven cancers from developing at all.

Additionally, he addressed practical considerations for treating clinicians: the feasibility of moving RAS inhibitors into earlier lines of therapy, and the biology oncologists, pharmacists, and genetic counselors should understand about differing KRAS allele subtypes.

McCormick is a professor in the Helen Diller Family Comprehensive Cancer Center and holds the David A. Wood Distinguished Professorship of Tumor Biology and Cancer Research at the University of California, San Francisco (UCSF). He has researched KRAS for 40 years and helped lead the NCI RAS Initiative. He was recently named the inaugural recipient of the Stephenson Global Prize from the Stephenson Global Pancreatic Cancer Research Institute.

Reference

Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines Inc. April 13, 2026. Accessed August 19, 2026. https://tinyurl.com/44t5vh5d