Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing
Abstract
:1. Introduction
2. DNMT Inhibitors
3. Drugs Targeting Histone Modifications
3.1. Histone Acetylation Modifiers
3.2. Targeting Histone Methyltransferases
4. Combining DNMTi and HDACi
5. Epigenetic Drugs and Chemotherapy
6. Epigenetic Drugs in Combination with Immunotherapy
7. Multitargeting Epigenetic Drugs
8. Targeting the Metabolic Causes of Epigenetic Changes—The Role of Oncometabolites
9. Epigenetic Editing
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Identifier | Study Title | Conditions | Epigenetic Drug | Other Anticancer Drug | Trial Phase | Estimated Enrollment |
---|---|---|---|---|---|---|
NCT04049344 | Decitabine Combined with Oxaliplatin in Patients with Advanced Renal Cell Carcinoma | Metastatic Renal Cell Carcinoma | Decitabine | Oxaliplatin | II | 25 |
NCT04510610 | Camrelizumab Plus Decitabine in Anti-PD-1 Treatment-naive Patients with Relapsed/Refractory Classical Hodgkin Lymphoma | Hodgkin Lymphoma | Decitabine | Camrelizumab | II/III | 100 |
NCT02159820 | Lower Dose Decitabine (DAC)-Primed TC (Carboplatin-Paclitaxel) Regimen in Ovary Cancer | Primary Malignant Neoplasm of Ovary; FIGO Stages II to IV | Decitabine | Carboplatin-Paclitaxel | II/III | 500 |
NCT04353479 | Combined PD1 Inhibitor and Decitabine in Elderly Patients with Relapse and Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia | Decitabine | Camrelizumab (SHR-1210) | II | 29 |
NCT03709550 | Enzalutamide and Decitabine in Treating Patients with Metastatic Castration Resistant Prostate Cancer | Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma in the Soft Tissue and 7 more | Decitabine | Enzalutamide | Ib/II | 21 |
NCT02957968 | Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca | Breast Adenocarcinoma; Estrogen Receptor-Negative Breast Cancer; Estrogen Receptor-Positive Breast Cancer and 10 more | Decitabine | Pembrolizumab followed by standard neoadjuvant chemotherapy | II | 32 |
NCT03295552 | Decitabine Plus Carboplatin in the Treatment of Metastatic TNBC | Metastatic Triple Negative Breast Cancer | Decitabine | Carboplatin | II | 59 |
NCT03094637 | Azacitidine and Pembrolizumab in Treating Patients with Myelodysplastic Syndrome | High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-1, Myelodysplastic Syndrome | Azacitidine | Pembrolizumab | II | 40 |
NCT04490707 | Study of Azacytidine Combined with Lenalidomide As Maintenance Therapy Based on MRD Monitoring in AML | Acute Myeloid Leukemia in Remission | Azacitidine | Lenalidomide | III | 60 |
NCT03019003 | Azacitidine, Durvalumab, and Tremelimumab in Recurrent and/or Metastatic Head and Neck Cancer Patients | Head and Neck Cancer | Azacitidine | Durvalumab, Tremelimumab | IB/II | 59 |
NCT03264404 | Azacitidine and Pembrolizumab in Pancreatic Cancer | Pancreas Cancer | Azacitidine | Pembrolizumab | II | 31 |
NCT03576963 | Guadecitabine and Nivolumab in Treating Refractory Metastatic Colorectal Cancer | Colorectal Adenocarcinoma, CpG Island Methylator Phenotype, Metastatic Microsatellite Stable Colorectal Carcinoma and 5 more | Guadecitabine | Nivolumab | IB/II | 45 |
NCT03308396 | Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer | Advanced Kidney Cancer, Kidney Cancer, Clear Cell Renal Cell Carcinoma | Guadecitabine | Durvalumab | IB/II | 58 |
NCT03913455 | Guadecitabine in Combination with Carboplatin in Extensive Stage Small Cell Lung Cancer | Small Cell Lung Cancer, Extensive-Stage Small Cell Lung Cancer | Guadecitabine | Carboplatin | II | 34 |
Identifier | Study Title | Conditions | Epigenetic Drug | Other Anticancer Drug | Trial Phase | Estimated Enrollment |
---|---|---|---|---|---|---|
NCT04651127 | A Phase Ib/II Trial of Anti-PD-1 Antibody Combined with Histone Deacetylase Inhibitor in Patients with Advanced Cervical Cancer | Cervical Cancer | Chidamide | Toripalimab | Ib/II | 40 |
NCT04562311 | Chidamide with Immunotherapy for Patients with Locally Advanced or Metastatic Urothelial Carcinoma | Bladder Cancer Stage IV | Chidamide | Tislelizumab | II | 43 |
NCT03820596 | Sintilimab in Combination with Chidamide in Refractory and Relapsed ENKTCL | Extranodal natural killer/T cell lymphoma | Chidamide | Sintilimab | I/II | 50 |
NCT03903458 | Tinostamustine and Nivolumab in Advanced Melanoma | Malignant Melanoma | Tinostamustine | Nivolumab | I | 21 |
NCT03024437 | Atezolizumab in Combination with Entinostat and Bevacizumab in Patients with Advanced Renal Cell Carcinoma | Metastatic Cancer, Renal Cancer | Entinostat | Atezolizumab and Bevacizumab | I/II | 62 |
NCT02616965 | A Study to Assess the Feasibility of Romidepsin Combined with Brentuximab Vedotin in Cutaneous T-cell Lymphoma | Cutaneous T-cell Lymphoma (CTCL) | Romidepsin | Brentuximab vedotin | I | 27 |
NCT03939182 | Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma | Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma | Abexinostat | Ibrutinib | I/II | 40 |
NCT03829930 | Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer | Prostate Adenocarcinoma | Entinostat | Enzalutamide | I | 18 |
NCT03848754 | Pracinostat and Gemtuzumab Ozogamicin (PraGO) in Patients with Relapsed/Refractory Acute Myeloid Leukemia | Relapsed Adult AML | Pracinostat | Gemtuzumab Ozogamicin | I | 18 |
NCT03742245 | Olaparib in Combination With Vorinostat in Patients with Relapsed/Refractory and/or Metastatic Breast Cancer | Relapsed/Refractory and/or Metastatic Breast Cancer | Vorinostat | Olaparib | I | 28 |
Drug Name | Year of FDA Approval | |
---|---|---|
DNMTi | Azacitidine | 2004 |
Decitabine | 2006 | |
HDACi | Vorinostat | 2006 |
Romidepsin | 2009 | |
Belinostat | 2014 | |
Panobinostat | 2015 | |
Chidamide * | 2015 |
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Majchrzak-Celińska, A.; Warych, A.; Szoszkiewicz, M. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing. Genes 2021, 12, 208. https://doi.org/10.3390/genes12020208
Majchrzak-Celińska A, Warych A, Szoszkiewicz M. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing. Genes. 2021; 12(2):208. https://doi.org/10.3390/genes12020208
Chicago/Turabian StyleMajchrzak-Celińska, Aleksandra, Anna Warych, and Mikołaj Szoszkiewicz. 2021. "Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing" Genes 12, no. 2: 208. https://doi.org/10.3390/genes12020208