EGFR, the Lazarus target for precision oncology in glioblastoma. Issue 12 (19th September 2022)

• Record Type: Journal Article
• Authors: Lin, Benjamin; Ziebro, Julia; Smithberger, Erin; Skinner, Kasey R; Zhao, Eva; Cloughesy, Timothy F; Binder, Zev A; O'Rourke, Donald M; Nathanson, David A; Furnari, Frank B; Miller, C Ryan
• Is Part Of: Neuro-oncology. Volume 24:Issue 12(2022)
• Page Start: 2035
• Page End: 2062
• Publication Date: 2022-09-19
• Subjects: Biological therapy -- glioblastoma -- molecular heterogeneity -- precision oncology -- tyrosine kinase inhibitors; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac204
• Languages: English
• ISSNs: 1522-8517

Abstract

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.