NOTCH1 (NOTCH transmembrane mechanosensitive receptor 1) signaling through Hes1 and Hes5 modulation has been identified as the primary regulator of asymmetric division, which directly influences heterogeneity-based chemoresistance by regulating the balance between intra-tumoral CRC stem cell populations [60]. This evidence concerns the gene HES1 and colorectal carcinoma.