Internal medicine

Autophagy

Bioinformatics

Biology

Cancer

Kinase

Apoptosis

Targeted therapy

Acquired resistance

MAPK/ERK pathway

Protein kinase A

Cancer research

Genetics

Medicine

Journal of Oncology

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.

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