Long-term exposure of glioma cell lines containing small stem cell populations to therapeutic stress (temozolomide) conferred differentiated glioma cells with stemness and pluripotency markers, such as CD133, SOX2, Oct4 and Nestin, whilst also upregulating HIF1/2α expression (Auffinger et al., 2014; Lee et al., 2016). This evidence concerns the gene NES and central nervous system cancer.