title: Targeted molecular therapies against epidermal growth factor receptor: past experiences and challenges.
abstract: Epidermal growth factor receptor (EGFR) has emerged as a highly attractive therapeutic target in glioblastoma (GBM) based on its high frequency of gene amplification and mutation and its identification as an upstream trigger of dysregulated cell signaling cascades that drive GBM pathophysiology. Extensive investment has been committed in an attempt to exploit EGFR therapeutically to improve outcome for GBM patients, including the development of a variety of EGFR-targeting therapeutics as well as the participation of hundreds of participants in multiple, carefully constructed clinical trials. In this review, we summarize the design and results of clinical trials evaluating EGFR tyrosine kinase inhibitors in recurrent and newly diagnosed GBM patients. While overall results thus far have been disappointing, it is premature to discount EGFR as a therapeutic target in GBM on the basis of these studies given the limitations in study design and the pharmacology of first-generation EGFR kinase inhibitors. Although important lessons have been learned, critical questions remain unanswered and warrant further study.
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors
keywords: EGFRvIII; epidermal growth factor receptor; glioblastoma; tyrosine kinase inhibitor