Erlotinib in Glioblastoma - Lost in Translation?

Georg      Karpel-Massler; M.      Andrew Westhoff; Richard      E. Kast; Christian      Rainer Wirtz; Marc-Eric      Halatsch

doi:10.2174/187152011797378788

Abstract

Glioblastoma represents the most common primary brain tumor in adults. Despite improvements of multimodal therapy, the prognosis of this disease remains unfavorable. Thus, great efforts have been made to identify therapeutic agents directed against those specific molecular targets whose presence was shown to be associated with worse clinical outcomes. The epidermal growth factor receptor (HER1/EGFR) has been identified as one such target, and different compounds were developed to inhibit HER1/EGFR and/ or its mutant form, EGFRvIII. However, clinical trials did not confirm the initial enthusiasm conveyed by promising results from experimental studies. Therefore, a therapeutic approach directed at inhibiting solely HER1/EGFR does not seem to translate into a clinical benefit. This review discusses the current therapeutic situation in the setting of glioblastoma while putting the spotlight on erlotinib, a HER1/EGFR-targeted small molecule tyrosine kinase inhibitor.

Keywords: Clinical trials, combination therapy, erlotinib, glioblastoma, HER1/EGFR, small molecule tyrosine kinase inhibitors, intracellular tyrosine kinase (TK) domain, phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, vascular endothelial growth factor (VEGF)