Fig. 3
From: Predictive biomarkers and potential drug combinations of epi-drugs in cancer therapy
Predictive biomarkers and drug combinations of histone deacetylation (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors. Prominent biomarkers and drug combinations of HDAC/DNMT inhibitors are detailed here. However, other biomarkers and HDAC/DNMT inhibitor combinations also exist. Me represents methylation. Ac represents acetylation. Similar to histone methylation, methylation of DNA occurs at cytosine residues and needs the participation of DNMT. Besides, histone acetylation has consistently been linked to a chromatin state and regulated by histone acetylases (HATs) and HDACs. The HDAC inhibitors include vorinostat, abexinostat, and panobinostat. The predicted biomarkers for the three HDAC inhibitors are Mcl-1, xCT, and Xist. Vorinostat combined with PFK 118–310 can effectively exert synergistic anticancer effects in breast cancer. Further, panobinostat combined with daratumumab can effectively exert synergistic anticancer effects in multiply myeloma. The DNMT inhibitors include 5'-azacytidine and decitabine. The 5'-azacytidine predicted biomarkers are the UCK1, DDIT3, and PMAIP1 status. The combination of 5'-azacytidine with a SMO inhibitor or AG-221 exerts improved anticancer effects in acute myeloid leukemia. Cellular hypoxia is a predictive biomarker for the selection of decitabine sensitive patients. In renal cell carcinoma, the combination between decitabine and the oxygen nanocarrier H-NPs exerts synergistic anticancer effects