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Comparing ERK signaling and Tumor Microenvironment in BRAF-altered Gliomas

Introduction

  • BRAF Class I and fusion alterations are two common oncogenic drivers in glioma 1 
  • The FDA has approved two regimens for the treatment of BRAF-altered glioma: a BRAF-V600E monomer inhibitor (dabrafenib) in combination with a MEK inhibitor (trametinib) or a pan-RAF inhibitor (tovorafenib)
  • However, the efficacy of BRAF inhibitors (BRAFi) is limited by intrinsic and acquired resistance • In other solid tumors, MAPK/ERK-dependence signatures have been identified that predict overall survival and response to BRAFi 2,3,4
  • The tumor immune microenvironment (TME) also mediates response to BRAFi and predicts survival in melanoma 5,6,7, 8, 9
  • However, it is unknown whether MAPK/ERK-dependence and TME signatures can predict survival and resistance to BRAFi in glioma 
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