HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity
Abstract
Simple Summary
Abstract
1. Introduction
1.1. HDAC Inhibitors in Cancer Therapy
1.2. Heterogeneity and Therapy Resistance
1.3. Epigenetic Drugs to Counter Tumor Heterogeneity and Overcome Resistance
2. Effects of HDAC Inhibitors and Therapeutic Implications for Tumor Heterogeneity
3. Dissecting the Variables of HDAC Inhibition
4. Conclusions
Treatment | HDACi | Drug Combination | Cancer Type | Phase | ID/Ref. |
---|---|---|---|---|---|
Monotherapy | Romidepsin | CRPC | II | [153] | |
SCLC | II | [265] | |||
Belinostat | Ovarian cancer | II | [154] | ||
Vorinostat | Solid tumors | II | [155] | ||
Ovarian cancer | II | [156] | |||
Panobinostat | AML | II | NCT00880269 | ||
Ricolinostat | Lymphoma, Lymphoid malignancies | Ib/II | NCT02091063 | ||
Maintenance | Panobinostat | AML, MDS | III | NCT04326764 | |
Chemotherapy | Romidepsin | CHOP | PTCL | III | NCT01796002 |
Vorinostat | Temozolomide | Glioma | I | NCT00268385 | |
Valproic acid | Epirubicin, 5-Fluorouracil, Cyclophosphamide | Solid tumors | I | NCT00246103 | |
PARPi | Entinostat | Olaparib | Ovarian, Peritoneal, Fallopian tube cancer | II | NCT03924245 |
Vorinostat | Olaparib | Breast Cancer | I | NCT03742245 | |
Endocrine therapy | Entinostat | Exemestane | HR+ & HER2- Breast cancer | III | NCT02115282 [9,266] |
Tucidinostat | HR+ & HER2- Breast cancer | III | NCT02482753 [8] | ||
EGFR TKI | Entinostat | Erlotinib | NSCLC | II | NCT00602030 [94] |
Vorinostat | Givinostat | NSCLC | I | NCT02151721 | |
Anti-angiogenic | Vorinostat | Bevacizumab | ccRCC | I/II | [204] |
Multiple | Panobinostat | Bortezomid & Dexamethasone | Multiple Myeloma | III | NCT01023308 [267] |
Entinostat | Nivolumab, Azacytidine | NSCLC | II | NCT01928576 | |
Romidepsin | Durvalumab, Azacytidine/Pralatrexate | Lymphoma | I/IIa | NCT03161223 | |
Ricolinostat | Pomalidomide, Dexamethasone | Multiple Myeloma | Ib/II | NCT01997840 | |
Citarinostat | PVX-410(cancer vaccine), Lenalidomide | Multiple Myeloma | I | NCT02886065 | |
Tucidinostat | rituximab-CHOP | MYC/BCL2 Double-Expressor DLBCL | III | NCT04231448 [268] | |
Vorinostat | Bevacizumab, Temozolomide, Radiotherapy | HGG | II/III | NCT01236560 |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Classification | Chemical Name | Targeted HDACs | FDA Approval |
---|---|---|---|
Cyclic depsipeptide | Romidepsin | Class I [10,11] | CTCL, PTCL [3,4] |
Largazole | Class I [11] | Under investigation | |
Hydroxamic acid | Trichostatin A(TSA) | Class I/II/IV [12,13] | Under investigation |
Vorinostat/SAHA | CTCL [1] | ||
Belinostat | PTCL [2] | ||
Panobinostat | MM [14] | ||
Benzamide | Entinostat | Class I [12,15] | Under investigation |
Chidamide/Tucidinostat | Class I [16] | PTCL (China) | |
Carboxylic acid | Valproic acid | Class I/IIa [17,18] | Under investigation |
Butyric acid | Class I/II | Under investigation |
Treatment | Cancer Type | Resistance Mechanism That Can Be Suppressed by HDACi |
---|---|---|
Chemotherapy | Solid tumor without targeted therapy option | Clonal transcriptional heterogeneity |
Glycolysis induction [74] | ||
PARP inhibition | HRR-deficient cancer | HRR activation [58] |
Checkpoint blockade inhibition | Lung, Bladder and more | Immune surveillance evasion [75] |
Tyrosine kinase inhibitor | EGFR+ Lung cancer | MET overexpression; EMT [55] |
Anti-estrogens | ER+ Breast cancer | Transcriptional Heterogeneity [71] |
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Karagiannis, D.; Rampias, T. HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity. Cancers 2021, 13, 3575. https://doi.org/10.3390/cancers13143575
Karagiannis D, Rampias T. HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity. Cancers. 2021; 13(14):3575. https://doi.org/10.3390/cancers13143575
Chicago/Turabian StyleKaragiannis, Dimitris, and Theodoros Rampias. 2021. "HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity" Cancers 13, no. 14: 3575. https://doi.org/10.3390/cancers13143575
APA StyleKaragiannis, D., & Rampias, T. (2021). HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity. Cancers, 13(14), 3575. https://doi.org/10.3390/cancers13143575