Fig. 1

Predictive biomarkers and drug combinations of histone methylation inhibitors. Prominent biomarkers and drug combinations of histone methyltransferase (HMT) and histone demethylase (HDM) inhibitors are detailed here. However, other biomarkers and drug combinations also exist. Histone octamer is the basic unit consisting of the nucleosome core particle. Me represents methylation. HMTs can methylate arginine or lysine of histone, meantime HDMs demethylates methylated histones. The small molecule drugs had been developed to inhibit HMT or HDM to regulate an epigenetic process in cancer cells. The application of these inhibitors acts as anticancer drugs by targeting individual biomarkers through different pathway in a variety of tumors. HMT inhibitors include the PRMT inhibitors GSK3368715 and GSK3326595 and the EZH2 inhibitors tazemetostat, CPI-1205, and GSK2816126. The predicted biomarkers for the two PRMT inhibitors are the MTAP and p53-MDM4 axes, respectively. GSK3326595 combined with immunotherapy can effectively exert synergistic anticancer effects in melanoma. The predicted biomarkers of the three EZH2 inhibitors are INI1, the PRC2 complex, and BRAF. The combination of CPI-1205 and an anti-CTL4 antibody can effectively exert a synergistic anticancer effect in melanoma. LSD1 inhibitors as HDM inhibitors include GSK2879552 and tranylcypromine. The DNA hypomethylation levels and ZEB2 status are predictive biomarkers for the selection of GSK2879552 sensitive patients. In hepatic carcinoma treatment, the combination of GSK2879552 and sorafenib exerts improved anticancer effects. In AML, the combination of tranylcypromine with mTORC1 inhibitors effectively exerts synergistic anticancer effects