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Response and resistance to BRAFV600E inhibition in gliomas: Roadblocks ahead?

Monica Capogiri1, Andrea J De Micheli1, Alvaro Lassaletta2

  • 1Department of Oncology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland.

Frontiers in Oncology
|January 26, 2023
PubMed

Insights

BRAF inhibitors offer new hope for BRAFV600E-mutated gliomas, but resistance remains a challenge. Understanding resistance mechanisms is key to improving targeted therapy outcomes for these brain tumors.

Area of Science:

  • Oncology
  • Neuro-oncology
  • Molecular Biology

Background:

  • BRAFV600E mutation is common in cancers, particularly pediatric low-grade gliomas (pLGG).
  • BRAF inhibitors (BRAFi) have transformed glioma treatment, but resistance limits efficacy.
  • Resistance to BRAFi and subsequent tumor growth are significant clinical hurdles.

Purpose of the Study:

  • To review current BRAFi achievements and limitations in glioma treatment.
  • To explore potential mechanisms of BRAFi resistance in BRAFV600E-mutated gliomas.
  • To discuss future directions for targeted therapy, leveraging resistance insights.

Main Methods:

  • Literature review of BRAF inhibition in gliomas.
  • Analysis of BRAFV600E mutation prevalence in CNS tumors.
  • Discussion of resistance mechanisms and therapeutic strategies.

Main Results:

  • BRAFi represent a paradigm shift in glioma care.
  • Intrinsic and acquired resistance to BRAFi are prevalent.
  • Predicting response and overcoming resistance are critical challenges.

Conclusions:

  • Further research into BRAFi resistance is essential for improving patient outcomes.
  • Targeted therapies for BRAFV600E gliomas require strategies to overcome resistance.
  • Understanding resistance mechanisms can guide future treatment development.
Keywords:
BRAF inhibitorsBRAFV600E mutationdrug resistancegliomahigh-grade glioma (HGG)low-grade glioma (LGG)

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