The hypoxic condition of BM and the availability of Notch ligands expressed by BM cells (Bertrand et al., 2000; Nefedova et al., 2004; Xu et al., 2012a; Jitschin et al., 2015; Colombo et al., 2016; Sato et al., 2016) suggest that Notch1 activation is not a limiting step in BM, and interestingly Notch1 activation promotes NSCLC CSC self-renewal via p-STAT3 and HES1 and induces resistance to cis-platinum treatment through the survival regulators p-AKT and survivin in a HES1-independent manner (Zhang Y. et al., 2017). This evidence concerns the gene HES1 and non-small cell lung carcinoma.