BRAF Mutations in CNS Tumors —Prognostic Markers and Therapeutic Targets

AbstractGliomas are a heterogeneous group of brain tumors with limited therapeutic options. However, identification ofBRAF V600E mutations in a subset of gliomas has provided a genomic-targeted approach for management of these diseases. In this review, we aimed to review the role ofBRAF V600E in gliomagenesis, to characterize concurrent genomic alterations and their potential prognostic implications, and to review comprehensively the efficacy data ofBRAF inhibitors (combined or not withMEK inhibitors) for the treatment of low- and high-grade gliomas. We also provide a summary of the toxicity of these agents and describe resistance mechanisms that may be circumvented by alternative genomic approaches. Although the efficacy of targeted therapy for management ofBRAF V600E-mutant gliomas has mostly been assessed in small retrospective and phase 2 studies with heterogeneous populations, the data generated so far are a proof of concept that genomic-directed therapies improve outcomes of patients with refractory/relapsed glioma and underpin the need of comprehensive genomic assessments for these difficult-to-treat diseases. In the future, the role of targeted therapy in the first-line setting and of genomic-directed therapies to overcome resistance mechanisms should be assessed in well-designed clinical trials.

Source: CNS Drugs - June 2, 2023 Category: Neurology Source Type: research