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Targeting KRAS is a desirable strategy because of the high prevalence of KRAS mutations and its importance in initiating and sustaining tumor growth. KRAS is the most commonly mutated member of the RAS family. KRAS mutations are seen in a variety of malignancies at different rates. Its incidence is highest in pancreatic cancers followed by colorectal cancer, NSCLC and cholangiocarcinoma. The profile of KRAS mutations differs significantly among diverse cancer types. 98% of KRAS mutations are found at G12, G13, or Q61. KRAS mutations occur in many cancers with different mutation frequencies, but there is also a large variation in mutation subtypes. The response to KRAS G12C inhibitors in patients is different, implicating the existence of resistance. Exploration of resistance should be conducted to identify biomarkers that indicate the appropriate population and tumor type in the clinical trial.
