Resistance mechanisms in BRAF^V600E paediatric high-grade glioma and current therapeutic approaches.

ABSTRACT: Paediatric high-grade gliomas (pHGG) are aggressive central nervous system tumours with a poor prognosis. BRAF^V600E mutant pHGGs can be treated with targeted BRAF inhibitors, which have shown both preclinical activity and potent clinical efficacy. Unfortunately, the development of drug resistance results in disease relapse or progression and is the primary cause of treatment failure. While there is a lot of data to explain mechanisms of resistance in other BRAF^V600E tumours, comparatively little is known about the mechanisms of BRAF inhibitor resistance in BRAF^V600E pHGG. Recent literature has identified aberrations in members of the RAS/RAF/ERK pathway, the PI3K/AKT/MTOR pathway and the cell cycle as major contributors to the resistance profile. A range of

SUBMITTER: Lehmann R 

PROVIDER: S-EPMC9792688 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature