Targeting KRAS mutation in gastrointestinal cancers

KRAS is the most commonly mutated gene in cancer and is associated with poor prognosis. Up to 44% of gastrointestinal cancers (GI) have KRAS mutations with the highest incidence observed in pancreatic cancer. Successfully targeting a specific mutation KRAS G12C in non-small cell lung cancer (NSCLC) has challenged the dogma that KRAS is a “non-druggable” target. With the advent of several RAS inhibitors, the opportunities for targeted therapy in GI cancers appears promising. This article provides in-depth review of KRAS mutations, and recently completed and ongoing clinical trials targeting KRAS mutations in GI cancers. In addition, this article reviews potential limitations for KRAS targeting in GI cancers.