Inhibitor MEKanisms

Roche's Genentech Inc. unit has figured out why different MEK inhibitors exhibit varying efficacy against BRAF- or K-Ras-driven cancers, which could help in the design of next-generation inhibitors with improved therapeutic indexes.¹ Genentech already has one inhibitor for each kind of tumor in clinical trials.

Mutations in the K-Ras (KRAS) and BRAF genes are responsible for overactivation of the Ras-Raf-MEK-MAPK pathway in many cancers. MEK is a key component of this signaling cascade, but for unknown reasons BRAF-mutant tumors thus far have been more sensitive than KRAS-mutant tumors to MEK inhibitors.²...