FAK inhibitor and RAF/MEK clamp avutometinib enhance KRAS G12C inhibitor efficacy in preclinical models of non-small cell lung cancer.

Combining FAK inhibitor and RAF/MEK clamp avutometinib with KRAS G12C inhibitor enhances tumor suppression in NSCLC models, overcoming resistance mechanisms.

• Why it matters: Resistance limits the effectiveness of KRAS G12C inhibitors in non-small cell lung cancer, necessitating new strategies to improve patient outcomes and durability of response.
• What they did: Researchers tested a triplet therapy of sotorasib, avutometinib, and defactinib in preclinical KRAS G12C NSCLC models, including resistant tumors, to evaluate synergistic effects on tumor growth.
• The result: The combination significantly increased tumor inhibition and restored sensitivity in resistant models, supporting clinical trials to target multiple pathways simultaneously for better treatment durability.