Endosomal acidification inhibitors for the treatment of BRAF mutant tumors.

Abstract

Mutations in KRAS and BRAF genes are commonly found in several types of cancer associated with poor prognosis and therapy resistance. We have identified phosphorylated p45-IKKα as an essential mediator of BRAF-induced tumorigenesis. Importantly, endosomal acidification inhibitors preclude phosphorylation of p45-IKKα and abolish the metastatic capacity of BRAF mutant cancer cells.