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Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors

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Technical Report,30 Sep 2014,29 Sep 2015

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Regents of the University of Colorado Aurora

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Despite advancement in treatment for childhood central nervous system CNS tumors, they remain the leading cause of death in pediatric oncology. One potential therapeutic intervention is targeting the autophagic pathway, a complex catabolic process that contributes to tumor cell survival. Recent data has shown BRAFV600E mutations in a range of these tumors and my own research finds that these tumors show a level of autophagy-dependence not seen in BRAFWT tumors. There is also evidence that autophagy inhibition is a potential mechanism in preventing or reversing resistance to direct inhibition against activated BRAFV600E. The current study examined the interaction of the BRAFV600E mutation and autophagy in brain tumors. I hypothesized that BRAFV600E identifies tumors that will respond to combination therapy with autophagy inhibition with enhanced tumor cell death, establishing a basis for future rational clinical trial design for pediatric brain tumor patients harboring the mutation.

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