Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma

Heterogeneous expression of the epidermal growth factor receptor (EGFR) in glioblastoma poses an important challenge for the effective use of EGFR-targeted therapies. In this Opinion article, Furnari et al . highlight the possible mechanisms underlying EGFR heterogeneity, and the importance in understanding these mechanisms to improve treatment outcome in glioblastoma. As tumours evolve, the daughter cells of the initiating cell often become molecularly heterogeneous and develop different functional properties and therapeutic vulnerabilities. In glioblastoma (GBM), a lethal form of brain cancer, the heterogeneous expression of the epidermal growth factor receptor (EGFR) poses a substantial challenge for the effective use of EGFR-targeted therapies. Understanding the mechanisms that cause EGFR heterogeneity in GBM should provide better insights into how they, and possibly other amplified receptor tyrosine kinases, affect cellular signalling, metabolism and drug resistance.