Targeting KRAS: Breakthrough Therapies for a Common Mutation

Ryan B. Corcoran, MD, PhD


December 14, 2020

Over the past three decades, Kirsten rat sarcoma viral oncogene homolog (KRAS) has come to be known as one of the most common mutated oncogenes in cancer. It is prevalent in non–small cell lung cancer and present to a lesser degree in colorectal and pancreatic cancers. The successful development of therapeutics to target this protein has proven futile primarily because KRAS lacks some of the typical binding pockets found in kinases and other druggable proteins.

A breakthrough came in 2013 when Jonathan M. Ostrem, and colleagues were able to target a variant of KRAS. They announced the development of small molecules that bind to a common oncogenic mutant, KRAS G12C.

Dr Ryan Corcoran, of Mass General Cancer Center in Boston, reports on the current clinical trials evaluating promising single agents such as sotorasib and adagrasib that target the KRAS G12C variant.

Dr Corcoran also highlights a promising clinical trial for a third therapy — BI 1701963 — that, instead of targeting KRAS G12C, targets molecules that directly interact with KRAS to disrupt its signaling pathway.


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