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November 1, 2025Neuro-OncologyOpen Access

Stem-23. GBM Neurodevelopmental Lineage Plasticity Drives Rapid Adaptation to Oncogene Targeted Therapy

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Authors

DCDimitri CadetTHToby HarrisEFElisa Fazzari

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Overview

Findings demonstrate that neurodevelopmental lineage plasticity drives adaptive cancer resistance in GBM, suggesting novel therapeutic strategies.

Key Points

  • This research aims to explore how neurodevelopmental lineage plasticity contributes to drug resistance in glioblastoma.
  • Used patient-derived GBM models
  • Applied global proteomics and single-cell RNA sequencing
  • Developed a novel lentiviral vector system (DENALI) for lineage tracking
  • Investigated effects of dual EGFR and RAS-MAPK inhibition
  • Identified lineage transition toward neuronal and OPC-like states after EGFR inhibition
  • Observed activation of RAS-MAPK signaling despite EGFR inhibition
  • Dual inhibition increased GBM cell death in EGFR-mutated models
  • Established neurodevelopmental lineage plasticity as key in adaptive resistance

Cite This Study

Cadet et al. (2025) studied this question.

synapsesocial.com/papers/69254366c0ce034ddc358451https://doi.org/10.1093/neuonc/noaf201.0330
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