EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.