EGFR, the Lazarus target for precision oncology in glioblastoma

Academic Article

Abstract

  • The Lazarus effect is a rare condition that happens when someone seemingly dead shows signs of life. The epidermal growth factor receptor (EGFR) represents a target in the fatal neoplasm glioblastoma (GBM) that through a series of negative clinical trials has prompted a vocal subset of the neuro-oncology community to declare this target dead. However, an argument can be made that the core tenets of precision oncology were overlooked in the initial clinical enthusiasm over EGFR as a therapeutic target in GBM. Namely, the wrong drugs were tested on the wrong patients at the wrong time. Furthermore, new insights into the biology of EGFR in GBM vis-à-vis other EGFR-driven neoplasms, such as non-small cell lung cancer, and development of novel GBM-specific EGFR therapeutics resurrects this target for future studies. Here, we will examine the distinct EGFR biology in GBM, how it exacerbates the challenge of treating a CNS neoplasm, how these unique challenges have influenced past and present EGFR-targeted therapeutic design and clinical trials, and what adjustments are needed to therapeutically exploit EGFR in this devastating disease.
  • Authors

    Published In

  • Neuro-Oncology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lin B; Ziebro J; Smithberger E; Skinner KR; Zhao E; Cloughesy TF; Binder ZA; O'Rourke DM; Nathanson DA; Furnari FB
  • Start Page

  • 2035
  • End Page

  • 2062
  • Volume

  • 24
  • Issue

  • 12