Targetting the EGFR Pathway in Glioblastoma Multiforme:

A Review of Current Pre-clinical and Clinical Trials with Tyrosine Kinase Inhibitors

Abstract

With a median overall survival expectancy of 15 months or less [FC17], Glioblastoma Multiforme (GBM) is the most common type of primary brain tumor [SA18]. Despite extensive research on the pathophysiology and clinical course of GBM, the malignancy remains one of the most lethal cancers to date as the 10 year survival rate is 0.71 percent [TT18]. While established methods of treatment such as resection, radiotherapy, and chemotherapy are effective in prolonging survival time, they are not effective in preventing recurrence [HL06] which occurs in almost every patient [OM14]. To better combat the dismal outcomes of GBM, novel approaches are necessary given the increase in incidence as well as the increase in tumor burden globally [GN20]. Gene therapy may serve as a promising novel therapeutic, with initial clinical studies indicating promising results [PK05]. This review will outline the most recent treatment protocols for differing GBM subtypes, characterize the tyrosine kinase epidermal growth factor receptor (EGFR) and its downstream signaling pathway, and analyze currently on-going and recently completed clinical trials involving tyrosine kinase inhibitors in GBM.