There are also multiple mechanisms of developing acquired resistance: (1) driver oncogene modification, e.g., development of EGFR T790M mutation, but not de novo alteration, is observed within 1 year in about 50% of NSCLC patients treated with the first and second generations of TKIs, resulting in tumor progression;43 (2) activation of independent pro-survival parallel signaling, e.g., cell proliferation, apoptosis, or autophagy and cell metabolism signaling;47 (3) adaption of the tumor microenvironment after the start of treatment. The gene discussed is EGFR; the disease is neoplasm.