These resistance mechanisms can be divided into three categories: 1) reactivation of the EGFR pathway through EGFR novel mutations; 2) activation of bypass signaling pathways; 3) histological shift able to bypass the EGFR-dependence in form of or small-cell lung cancer (SCLC) transformation (99–101). The gene discussed is EGFR; the disease is small cell lung carcinoma.