Loss of responsiveness to EGFR-TKIs in NSCLC with non-T790M EGFR mutation can be explained in terms of EGFR-TKI-resistant ALDH1A1bright/CD44high CSC that evolutionally possesses drug resistance and is often referred to as a tumor-initiating cell and associated with EGFR-TKIs non-responder [12, 17, 28]. This evidence concerns the gene EGFR and non-small cell lung carcinoma.