Table 1 Effect of regulating HMTs on drug resistance in tumors
From: Histone methyltransferase and drug resistance in cancers
Enzyme | Cancer type | Drug | Inhibitor | Mechanism (Reference) |
|---|---|---|---|---|
EZH2 | Clear cell renal cell carcinoma | Sunitinib | EPZ011989 | Reduced overall phosphorylation of kinases and increased activation of tumor suppressors [90]. |
| Â | Ovarian cancer | Cisplatin | GSK126 | Increased copper transporter 1 & platinum accumulation [91, 92]. |
| Â | SCLC | Etoposide | GSK126 | Reduced H3K27me3 in CDKN1C promoter, leading to increased CDKN1C expression [93]. |
| Â | Melanoma | Immune checkpoint inhibitors | GSK503 | Decreased H3K27me3 leads to up-regulation of antigen and down-regulation of PD-L1 [94]. |
G9a | NSCLC | EGFR-TKI | UNC0638 | Regulation of PTEN / AKT pathway is inhibited [68]. |
| Â | HNSCC | Cisplatin | UNC0638 | H3K9me1 reduction in GCLC promoter causes an increase in Glutathione expression [65]. |
| Â | GBM | Temozolomide | BIX-01294 | Unknown [95]. |
| Â | Cervical cancer | Gemcitabine | Hydralazine | H3K9me2 decreases in hENT1 and deoxyeytidine kinase promoters [96]. |
| Â | Hepatocellular Carcinoma | TRAIL | BIX-01294 | Downregulate Survivin [97]. |
SETD2 | Acute leukemia | Cytarabine, Etoposide | JIB-04 | Reduced H3K36me3 in exons of LEDGF and MSH6 related proteins [99,100,101]. |
DOT1L | Breast cancer | Antiestrogen | EPZ004777 | Blocked ERα expression [102]. |
MLL1 | Pancreatic cancer | PD-L1 inhibitor | Verticillin A | Reduced H3K4me3 in the CD274 promoter and PD-L1 expression [103]. |
PRMT5 | Breast cancer | CDK4/6 inhibitor (palbociclib) | GSK3326595 | Reduced MDM4 expression leads to p53 activation and the inhibition of CDK2 [104]. |
| Â | GBM | mTOR inhibitors | EPZ015666 | Inhibited SDMA methylation in hnRNP A1 and IRES-mediated activation of related proteins [84]. |