Table 2 Key clinical trials of epigenetic therapies across cancer types
From: Epigenetic regulators in cancer therapy and progression
Drug | Target | Cancer Type(s) | Clinical Trial Phase | Outcomes | Limitations | References |
|---|---|---|---|---|---|---|
Vorinostat (SAHA) | HDAC inhibitor | Cutaneous T-cell lymphoma (CTCL), solid tumors | Approved (CTCL); Ongoing trials (solid tumors) | FDA-approved for CTCL (2006); partial responses in solid tumors, but limited durable efficacy | Off-target effects: fatigue, thrombocytopenia, gastrointestinal toxicities | Duvic et al.205 |
Azacitidine (Vidaza) | DNMT inhibitor | Myelodysplastic syndromes (MDS), AML | Approved (MDS); Ongoing (AML) | Improved overall survival in MDS; modest benefit in elderly AML patients | Myelosuppression; infection risk; limited effect in rapidly proliferating AML | Fenaux et al.189 |
Decitabine | DNMT inhibitor | MDS, AML | Approved (MDS); Ongoing (AML) | Improved response rates in older AML; approved for MDS | Hematologic toxicities (neutropenia, anemia); infection | Garcia-Manero et al.206 |
Tazemetostat (Tazverik) | EZH2 inhibitor | Follicular lymphoma, epithelioid sarcoma | Approved (2020) | Durable objective responses in relapsed/refractory follicular lymphoma and advanced epithelioid sarcoma | Resistance emergence; secondary malignancies; fatigue, nausea | Hoy, 2020191 |
Belinostat | HDAC inhibitor | Peripheral T-cell lymphoma (PTCL) | Approved (2014) | Accelerated approval for PTCL; ~26% overall response rate | Hematologic toxicity; infections; fatigue | O’Connor et al.207 |
Entinostat | HDAC inhibitor | Breast cancer, NSCLC | Phase III (ongoing) | Shown to sensitize tumors to immune checkpoint inhibitors; improvement in PFS in combination with endocrine therapy | Side effects include neutropenia, fatigue; requires combination for maximal efficacy | Yardley et al.208 |
CC-486 (oral Azacitidine) | DNMT inhibitor | AML, MDS | Approved (2020) | Maintenance therapy post-AML remission; prolongs survival | Gastrointestinal events; cytopenias | Wei et al.209 |
Valemetostat | Dual EZH1/2 inhibitor | Adult T-cell leukemia/lymphoma (ATLL) | Phase II (completed) | Promising efficacy in relapsed/refractory ATLL; ORR ~ 48% | Potential for epigenetic reprogramming resistance; hematologic adverse events | Zinzani, et al.210 |
Guadecitabine | DNMT inhibitor (next-gen) | AML, MDS | Phase III (discontinued) | Failed to significantly improve OS in Phase III AML trial | Lack of survival benefit; adverse effects similar to earlier DNMT inhibitors | Fenaux et al.211 |
