Review on targeting MEK in cancer and beyond
A publication in The Lancet reviews mechanistic insights and therapeutic opportunities of targeting MEK in cancer and beyond. MEK inhibitors are established therapies in BRAF-driven cancers, yet their broader clinical effect is limited by toxicity, resistance, and modest durability as a monotherapy, particularly in RAS-mutant tumors. Dose intensity is often restricted by severe adverse effects. Predictive biomarkers are emerging as crucial tools for refining patient selection and monitoring therapeutic response. Combination regimens, particularly those incorporating immune checkpoint inhibitors or PI3K-mTOR pathway inhibition, show promise for enhancing efficacy and treatment durability. Beyond oncology, MEK pathway modulation is under investigation in fibrotic, inflammatory, and developmental disorders, although clinical validation remains at an early stage. Buidling on more than a decade of use in BRAFV600-mutant melanoma, MEK inhibitors continue to be refined through biomarker-guided combination strategies and exploration in additional cancers and non-oncological diseases.