EGFR and non-small cell lung carcinoma: In EGFR-mutant NSCLC, resistance to TKIs encompasses a spectrum of multilayered biological processes, including the emergence of secondary mutations within the receptor tyrosine kinase domain, activation of alternative receptor tyrosine kinases through amplification or rearrangement, reprogramming of intracellular signaling networks, and phenotypic histologic transformation of tumor cells.