Table 2.
Receptor-based epigenetic therapy and mechanisms for endocrine-related diseases.
| Epigenetic therapeutic targets | Epigenetics drugs | Therapeutic mechanisms | Reference |
|---|---|---|---|
| AF1 | Tamoxifen | Disrupts receptors' competition with E2 for ERα binding and hinders ERα-LBD coactivator recruitment | 123 |
| KMT2D SMYD2 |
PI3Kα/AKT inhibitors SMYD2 inhibitors |
Sensitizes BC to PI3K/AKT inhibition and endocrine therapy, in part through KMT2D K1330 methylation | 125,128 |
| DNMT | Decitabine, 5-azacytidine | Suppressed the ethylation of PPARγ1 promoter DNA, enhancing macrophage activation | 129,130 |
| Enterestat and letrozole | Restored ER-α and enzyme expression in ER-BC cell lines, leading to growth inhibition | 132 | |
| Fulvestrant | Sensitized ER-positive BC cells to ferroptosis through down-regulating MBOAT1 | 135 | |
| FOXA1/GRHL2 | LYPD3 inhibitors | Inhibits proliferation of endocrine-resistant tumors | 72 |
| KAT6A/KAT6B | KAT6A/6B HAT inhibitors | Blocks histone modification, showing anti-tumor activity in ER-positve BC | 69 |
| LATS | LATS inhibitors (VT02956) | Suppresses ESR1, controlling ER-positve BC growth via Hippo pathway | 139 |
| CDK4/6 AKT |
CDK4/6 inhibitors (abemaciclib) AKT inhibitors (capivasertib) |
Reverses endocrine resistance with fulvestrant | 140,141 |
| ER coregulator | ERX-11 | Binds to ER, modulates coregulator interactions, and inhibits BC proliferation | 142 |
| DMA | Increases ER-β mRNA levels in endometrium | 156 | |
| IL-1β, TGF-β | Inhibits DNMT1 +32204 GG genotype remission in patients with Graves' disease | 105 | |
| KDM4 and KDM1 | Induces PC cells apoptosis | 145 | |
| BRD4 | Obstructs AR binding and transcriptional activity | 146 | |
| EZH2 | SETD2 | Blocks PC metastasis by methylation and EZH2 degradation (SETD2) | 150 |
| FOXA1 | Provides treatment strategy for CRPC via AR cis-antigenome impact | 152 | |
| Hsp70 | Hsp70 inhibitors | Binds to AR N-terminal domain and reduces AR expression and transcriptional activity | 151 |
| TET2 | TET2 inhibitors | Eliminates resistance in ZNF397-deficient tumors to AR therapy | 153 |
| HDAC | MS-275 | Regulates genes in glucose and lipid metabolism | 158 |
| OPN and RUNX2 | Decitabine | Promotes osteogenic differentiation by reducing methylation | 160 |
| Histone 4 | Vorinostat | Enhances regulation and phosphorylation of insulin receptor β, AKT, and FOXO1 | 161 |
| P300 acetyltransferase | C646 | Blocks IRS1/2 acetylation and aids IRS1/2 membrane movement | 162 |
| GLP1R | Rivenatide | Suppresses 12 CpG sites methylated at GLP1 transcription start | 163 |
Note: AKT, protein kinase B; AR, androgen receptor; BRD4, bromodomain-containing protein 4; CDK, cyclin-dependent kinases; DNMT, DNA methyltransferases; DMA, demethylating agent; ERXs, estrogen receptor coregulator binding modulators; EZH2, enhancer of zeste homolog 2; ER, estrogen receptor; ERα-LBD, estrogen receptor-α ligand binding domain; FOXO1, Forkhead box O1; FOXA1, Forkhead box A1; GRHL2, Grainyhead like 2; GLP1, glucagon-like peptide-1; GLP1R, glucagon-like peptide-1 receptor; HDAC, histone deacetylase; IL-1β, interleukin-1beta; IRS1/2, insulin receptor substrate 1/2; KDM, histone lysine demethylase; LYPD3, LY6/PLAUR domain containing 3; LATS, large tumor suppressor kinase; MBOAT1, membrane-bound O-acyltransferase domain-containing 1; PPARγ1, peroxisome proliferator-activated receptor gamma 1; RUNX2, Runt-related transcription factor 2; SETD2, SET domain-containing 2; TGF-β, transforming growth factor-beta.