TABLE 3.
Epigenetic modification, targets, and drugs in cancer.
| Targets | Drugs | Mechanism | Cancer type | Clinical trial | Phase | Status | References |
|---|---|---|---|---|---|---|---|
| DNMT | 5‐Azacytidine (Vidaza) | Reversing hypermethylation to restore transcription of tumor suppressor genes | Squamous cell carcinoma, head and neck cancer | NCT05317000 | I | Recruiting | 221 |
| SGI‐110 (guadecitabine) | The precursor drug of decitabine/ extending drug exposure | Leukemia | NCT02907359 | III | Completed | 210 | |
| Decitabine (Dacogen) | Inhibit DNA methylation of tumor suppressor genes | Pancreatic cancer | NCT05360264 | II | Recruiting | 222 | |
| HDAC | Vorinostat (Zolinza) | Modulating chromatin conformation, inducing cellular differentiation, and blocking cell cycle | Rhabdomyosarcom | NCT04308330 | I | Recruiting | 223 |
| Belinostat | Inducing accumulation of acetylated histones and apoptosis‐related proteins | Refractory peripheral T‐cell lymphoma | NCT05170334 | II | Recruiting | 224 | |
| Citarinostat | Decreasing Th2 cytokine production (i.e., IL‐4, IL‐5, IL‐6, IL‐10, and IL‐13) | Smoldering multiple myeloma | NCT02886065 | I | Recruiting | 225 | |
| Entinostat | Promoting immune editing of tumor neoantigens and remodeling the tumor immune microenvironment | Breast cancer | NCT02115282 | III | Recruiting | 226 | |
| Valproic acid | Inducing proteasomal degradation of HDAC2 | Non‐small‐lung cancer | NCT01203735 | II | N/A | 227 | |
| Trichostatin A | Inhibiting dendritic cell maturation andadipogenesis | Hematologic malignancies | NCT03838926 | I | N/A | 228 , 229 | |
| Tacedinaline (CI‐994) | Suppressing NF‐κB pathway | Lung cancer | NCT00005093 | III | Completed | 230 | |
| Panobinostat (Faridak) | Modulating chromatin conformation, facilitating transcription, and inhibiting protein metabolism | Multiple myeloma | N/A | N/A | Approved (US FDA) | 231 | |
| Romidepsin (Istodax) | Inducing cell death | Cutaneous T‐cell lymphoma | N/A | N/A | Approved (US FDA) | 232 | |
| Chidamide | Inducing growth arrest and apoptosis and enhancing antitumor immunity | Peripheral T‐cell lymphoma | N/A | N/A | N/A | 233 | |
| HMTs | Tazemetostat | Competitively inhibiting the methylation of histone lysine | Relapsed or refractory follicular lymphoma | NCT01897571 | II | Completed | 234 |
| Pinometostat | Reducing H3K79 methylation | Acute myeloid leukemia | NCT03701295 | II | Completed | 235 | |
| GSK126 | Suppressing antitumor immunity by driving production of myeloid‐derived suppressor cells | Leukemia | N/A | N/A | N/A | 236 | |
| AZ505 | Inhibiting the binding of SMYD2 to miR‐125b promoter | Renal cell carcinoma | N/A | N/A | N/A | 237 | |
| EPZ015666 | Inhibiting EMT by promoting expression of TET1 and increasing 5hmC | Cervical cancer | N/A | N/A | N/A | 238 | |
| MS023 | Activation of interferon responses | Breast cancer | N/A | N/A | N/A | 239 | |
| HDMs | GSK2879552 | Inducing the expression of KDM1A‐targeted genes to counteract cell proliferation | Leukemia | NCT02177812 | I | Terminated | 240 |
| Seclidemstat (SP‐2577) | Suppressing the viability and metabolism of NK cells | Chronic myelomonocytic leukemia | NCT04734990 | II | Recruiting | 241 | |
| JIB‐04 | Inducing cell apoptosis | Liver cancer | N/A | N/A | N/A | 242 | |
| GSK‐J4 | Inhibiting the JMJD3/UTX enzyme to upregulate H3K27me3 level | Acute myeloid leukemia | N/A | N/A | N/A | 243 | |
| ZY0511 | Inducing H3K4 methylation at the promoter of GADD45B | Hepatocellular carcinoma | N/A | N/A | N/A | 244 |
Abbreviations: DNMT, DNA methyltransferases; HDAC, histone deacetylases; HMTs, histone methylases; HDMs, histone demethylases.