Mechanisms of EGFR Resistance in Glioblastoma
Peter Pan, Rajiv Magge
Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite numerous efforts to target epidermal growth factor receptor (EGFR), commonly dysregulated in GBM, approaches directed against EGFR have not achieved the same degree of success as seen in other tumor types, particularly as compared to non-small cell lung cancer (NSCLC). EGFR alterations in glioblastoma lie primarily in the extracellular domain, unlike the kinase domain alterations seen in NSCLC. Small molecule inhibitors are difficult to develop for the extracellular domain. Monoclonal antibodies can be developed to target the extracellular domain but must contend with the blood brain barrier (BBB). We review the role of EGFR in GBM, the history of trialed treatments, and the potential paths forward to target the pathway that may have greater success.