EGFR and cancer: Additional genetic alterations within the target oncogene itself, which prevent drug binding and lead to kinase activation even in the presence of the inhibitor, are a common mechanism of both primary and acquired resistance in cancer; a paradigmatic example is provided by the T790M “gatekeeper” secondary mutation in the EGFR gene, which installs resistance to reversible EGFR inhibitors in EGFR-mutant NSCLC [108].