alexa Epidermal growth factor receptor: a re-emerging target in glioblastoma.


Journal of Brain Tumors & Neurooncology

Author(s): Hegi ME, Rajakannu P, Weller M

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Abstract PURPOSE OF REVIEW: Amplification and overexpression of the epidermal growth factor receptor (EGFR) gene are a hallmark of primary glioblastoma (45\%), making it a prime target for therapy. In addition, these amplifications are frequently associated with oncogenic mutations in the extracellular domain. However, efforts at targeting the EGFR tyrosine kinase using small molecule inhibitors or antibodies have shown disappointing efficacy in clinical trials for newly diagnosed or recurrent glioblastoma. Here, we review recent insights into molecular mechanisms relevant for effective targeting of the EGFR pathway. RECENT FINDINGS: Molecular workup of glioblastoma tissue of patients under treatment with small molecule inhibitors has established drug concentrations in the tumor tissue, and has shed light on the effectiveness of target inhibition and respective effects on pathway signaling. Further, functional analyses of interaction of small molecule inhibitors with distinct properties to bind to the active or inactive form of EGFR have provided new insights that will impact the choice of drugs. Finally, vaccination approaches targeting the EGFRvIII mutant featuring a tumor-specific antigen have shown promising results that warrant larger controlled clinical trials. SUMMARY: A combination of preclinical and clinical studies at the molecular level has provided new insights that will allow refining strategies for targeting the EGFR pathway in glioblastoma. This article was published in Curr Opin Neurol and referenced in Journal of Brain Tumors & Neurooncology

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