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BRAF alterations in primary brain tumors

Stefania Maraka1, Filip Janku2

  • 1Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Discovery Medicine
|September 29, 2018
PubMed

Insights

BRAF gene alterations are implicated in primary brain tumors. BRAF inhibitors show promise for treating specific mutations like BRAF-V600E, but caution is advised for KIAA1549-BRAF fusions.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Primary brain tumors can exhibit alterations in the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene.
  • The BRAF protein is a key component of the Ras-Raf-MEK-ERK signaling pathway, regulating cell division and differentiation.

Purpose of the Study:

  • To review the role of BRAF alterations in primary brain tumors.
  • To discuss the therapeutic potential and challenges of BRAF inhibitors (BRAFi) in neuro-oncology.

Main Methods:

  • Literature review of studies on BRAF alterations in primary brain tumors.
  • Analysis of clinical trial data and case reports regarding BRAFi efficacy and resistance.

Main Results:

  • BRAF-V600E mutations are prevalent in specific tumor types (e.g., pleomorphic xanthoastrocytoma) and younger patients.
  • BRAF-KIAA1549 fusion is common in pilocytic astrocytoma.
  • First-generation BRAFi show activity in brain metastases and are in trials for pediatric tumors with BRAF-V600E mutations.

Conclusions:

  • BRAFi represent a potential targeted therapy for primary brain tumors with specific BRAF alterations.
  • Combination therapies and second-generation BRAFi are being developed to overcome resistance and improve safety.
  • First-generation BRAFi should not be used for tumors with KIAA1549-BRAF fusion due to paradoxical pathway activation.

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