Moreover, Lee et al.[68] have found that temozolomide (TMZ)-triggered HIF1α/HIF2α upregulation plays a major role in converting non-stem glioma cells to stem-like cells, and that knockdown of HIF1α/HIF2α inhibited the conversion of non-stem glioma cells to glioma stem cells (GSCs) post-therapy[68]. This evidence concerns the gene EPAS1 and central nervous system cancer.