HES5 and hepatocellular carcinoma: Ankur Sharma et al. reported the upregulation of NOTCH2, DLL4, and HES1 in HCC samples.[26] Sarah Luiken et al. revealed that the Notch target gene HES5 exerts tumor-suppressive effects by inhibiting HES1 and downregulating the pro-proliferative MYC target genes, such as ODC1 and LDHA.[27] In contrast, HES5 promoted oncogenesis by disrupting the formation of AKT-dependent liver cancer.