Overcoming Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutated Tumours

J Oncol. 2020 Jan 3:2020:1079827. doi: 10.1155/2020/1079827. eCollection 2020.

Abstract

Overactivation of the mitogen-activated protein kinase (MAPK) pathway is an important driver of many human cancers. First line, FDA-approved therapies targeting MAPK signalling, which include BRAF and MEK inhibitors, have variable success across cancers, and a significant number of patients quickly develop resistance. In recent years, a number of preclinical studies have reported alternative methods of overcoming resistance, which include promoting apoptosis, modulating autophagy, and targeting mitochondrial metabolism. This review summarizes mechanisms of resistance to approved MAPK-targeted therapies in BRAF-mutated cancers and discusses novel preclinical approaches to overcoming resistance.

Publication types

  • Review