Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma
Abstract
:1. Introduction
2. HDACi Clinical Trials for Uveal Melanoma and/or Metastatic Uveal Melanoma
3. Selective HDAC6i as a Therapeutic Option for Uveal Melanoma
4. Involvement of HDAC6 in Tumor Growth, Survival and Progression
5. Immunomodulatory Effects of HDAC6 Inhibitors
6. Is HDAC6 Expression Disease-Relevant in Uveal Melanoma Tissues?
7. Highly Effective Anti-Cancer Activity of HDAC6 Inhibitors Achieved at Non-HDAC6 Selective Concentrations
8. Future Perspectives
8.1. Drug Synergism as a Strategic Approach to Treat MUM
8.2. Can Extracellular Vesicles Be Exploited as Therapeutic Options in UM/MUM?
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | HDAC Class | Clinical Trial Identifier | Phase | Status |
---|---|---|---|---|
Entinostat + Pembrolizumab | Class I | NCT02697630 | II | Ongoing |
NCT03765229 | II | Recruiting | ||
Vorinostat | Pan-HDAC | NCT00121225 | II | Completed |
NCT01587352 | II | Ongoing | ||
NCT03022565 | - | Withdrawn | ||
Valproic acid | Pan-HDAC | NCT02068586 | II | Ongoing |
Belinostat + Binimetinib | Pan-HDAC | NCT05170334 | II | Recruiting |
Cancer Type | Drug Combination | Clinical Trial Identifier(s) | Phase | No. of Participants | Status | Outcome | Reference (PMID) |
---|---|---|---|---|---|---|---|
Biliary Tract Cancer (advanced) | KA2507 | NCT04186156 EUCTR2019-001459-38-GB | Ib/II | N/A | Withdrawn | N/A | |
Relapsed/Refractory Multiple Myeloma | ACY-1215 + Bortezomib/Dexamethasone | NCT01323751 | I/II | 120 | Completed | N/A | |
Lymphoid Malignancies, Lymphoma | ACY-1215 | NCT02091063 | I/II | 24 | Completed | Under review | |
Non-Small Cell Lung Cancer | ACY-241 + Nivolumab | NCT02635061 | Ib | 17 | Active, not recruiting | Ongoing | 34552864 |
Solid Tumor, Adult | KA2507 | NCT03008018 | I | 20 | Completed | Published | 33947698 |
Metastatic Breast Cancer, Breast Carcinoma | ACY-1215 + Nab-paclitaxel | NCT02632071 | Ib | 17 | Completed | N/A | |
Unresectable/Metastatic Cholangiocarcinoma | ACY-1215 + Gemcitabine/Cisplatin | NCT02856568 | Ib | N/A | Withdrawn | N/A | |
Relapsed/Refractory Multiple Myeloma | ACY-1215 + Pomalidomide/Dexamethasone | EUCTR2014-002338-29-IT EUCTR2014-002338-29-GR NCT01997840 | Ib/II | 103 | Active, not recruiting | Ongoing | |
Gynecological Cancer | ACY-1215 + Paclitaxel/Bevacizumab | NCT02661815 | Ib | 6 | Terminated | Available | |
Malignant Melanoma | ACY-241 + Nivolumab + Ipilimumab | NCT02935790 | Ib | 1 | Completed | N/A | |
Solid Tumor (advanced) | JBI-802 | NCT05268666 | I/II | 126 | Recruiting | N/A |
Cancer Cell Line(s) | HDAC6 Inhibitor | Reported IC50 Value | Concentration Used | Reference (PMID) |
---|---|---|---|---|
HAP1-KO (HDAC6) | Tubathian A (8A) | 1.9 nM | 1, 10 and 50 µM | 30694564 |
Tubastatin A (Tub A) | 15 nM | 1, 10 and 50 µM | ||
Tubacin (Tub) | 4 nM | 1 and 10 µM | ||
Ricolinostat (ACY-1215) | 4.7 nM | 1 and 10 µM | ||
A375 HDAC6-KO DLD1 HDAC6-KO MDA-MB-231 HDAC6-KO TOV-21G HDAC6-KO | Ricolinostat (ACY-1215) Citarinostat (ACY-241) | 4.7 nM | 0.1–100 µM | 31511426 |
2.6 nM | ||||
SMG5 and SMG6 | Ricolinostat (ACY-1215) | 4.7 nM | 0–50 µM | 33322608 |
Mel270, Mel285 and OMM2.5 | Ricolinostat (ACY-1215) | 4.7 nM | 1–50 µM | 35159049 |
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Sundaramurthi, H.; Giricz, Z.; Kennedy, B.N. Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma. Int. J. Mol. Sci. 2022, 23, 9378. https://doi.org/10.3390/ijms23169378
Sundaramurthi H, Giricz Z, Kennedy BN. Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma. International Journal of Molecular Sciences. 2022; 23(16):9378. https://doi.org/10.3390/ijms23169378
Chicago/Turabian StyleSundaramurthi, Husvinee, Zoltán Giricz, and Breandán N. Kennedy. 2022. "Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma" International Journal of Molecular Sciences 23, no. 16: 9378. https://doi.org/10.3390/ijms23169378