Spectrum of acquired resistance mechanisms. Frequencies of acquired resistance mechanisms under reversible (a) and irreversible (b) EGFR TKI therapy. The EGFR p. T790M gatekeeper mutation ist the major mechanism of resistance in reversible as well as irreversible EGFR TKI treated patients. Frequencies of alternative resistance mechanisms besides p.T790M are comparable. Note, section p.T790M covers only patients with T790M as exclusive resistance mechanism. Section of multiple resistance mechanisms includes patients with p.T790M plus MET or HER2 amplification.