Differential Response and Resistance to KRAS-Targeted Therapy - PubMed

8 days ago

KRAS is the most frequently mutated oncogene in epithelial malignancies like lung, colorectal, and pancreatic tumors (25-90% cases).
KRAS was considered undruggable for decades until the development of covalent inhibitors targeting the KRAS G12C mutant.
Sotorasib and adagrasib are recently approved KRAS G12C inhibitors, marking a new era in KRAS-targeted therapy.
A major challenge is intrinsic and acquired resistance to KRAS inhibitors, with many patients not responding to treatment.
Colorectal cancer shows a lower response rate to KRAS G12C inhibitors compared to non-small cell lung cancer.
Therapeutic responses to KRAS G12C inhibition are often short-lived due to rapid emergence of acquired resistance.
The review summarizes mechanisms of resistance in colorectal, lung, and pancreatic cancers and discusses combination strategies to overcome resistance.

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