Abstract
RAF- and MEK-targeted therapies are approved for patients with BRAF(V600E) melanoma and under investigation in a several other tumor types, but resistance remains a major challenge. We uncovered yes-associated protein 1 (YAP1) as a mechanism of resistance to RAF-MEK inhibition in BRAF- and RAS-mutant cancers, providing a rationale for co-targeting YAP and RAF-MEK to enhance patient outcomes.