LCSCs from WT-EGFR NSCLC patients with SCC (n=3), adenocarcinoma (ADC, n=3) and large-cell neuroendocrine carcinoma (LCNEC, n=1; Table 1a) were isolated as tumor spheres in serum-free culture conditions that enrich cultures for undifferentiated tumor cells endowed with stem cell properties of long-term proliferation capacity, increased clonogenic potential, differentiation ability, chemoresistance, increased tumorigenicity and ability to generate xenografts that mimic the tumor of origin, as we previously reported24, 32, 33 and have shown in Figure 1. This evidence concerns the gene EGFR and large cell neuroendocrine carcinoma.