Occupy EGFR.

Erlotinib and gefitinib inhibit the growth of non-small cell lung cancer tumors that harbor activating epidermal growth factor receptor (EGFR) mutations but are ineffective against EGFR variants found in glioblastoma. New studies by Barkovich and colleagues and Vivanco and colleagues show that these drugs only occupy the active sites of glioblastoma-derived EGFR mutants to a limited extent and fail to inhibit the activated receptor. Other EGFR inhibitors that target distinct receptor conformations are more effective in the treatment of glioblastoma. These studies reveal distinct drug selectivities for different EGFR mutations and show that an analysis of binding-site occupancy should be considered as a biomarker for inhibitor efficacy in targeting EGFR.