Targeted Therapy for MAPK Alterations in Pediatric Gliomas.

Abstract

Although the mitogen-activated protein kinase (MAPK) pathway helps promote normal cell development, the pathway is known to contribute to the initiation and growth of many types of cancers. Tumorigenesis can result from mutations in a number of the pathway's key proteins, including but not limited to RAS, any one of the three RAF kinases, or MEK1/2. Moreover, by discovering and understanding the biology of oncogenic mutations, scientists can develop novel targeted therapies. This review describes the general history of such targeted therapies in the context of pediatric gliomas. We first describe the biology of gliomas and oncogenic mutations in the MAPK pathway and then summarize notable pre-clinical data and clinical trials for these targeted therapies.