Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies
Abstract
1. Introduction
2. Epigenetic Landscape of Bone Metastasis
2.1. DNA Methylation and Bone Metastasis
2.2. Histone Modifications and Bone Metastasis
2.2.1. Histone Acetylation
2.2.2. Histone Methylation
2.3. Chromatin Remodeling and Bone Metastasis
2.4. Non-Coding RNAs and Bone Metastasis
2.4.1. Long Non-Coding RNAs (lncRNAs)
2.4.2. MicroRNAs (miRNAs)
2.4.3. Circular RNAs (circRNAs)
2.4.4. Epitranscriptomic Modifications
2.5. Epigenetic Interactions with Bone-Resident Cells
2.6. Epigenetic Modulation of Bone Homeostasis
2.7. Epigenetics of Dormancy and Lesion Heterogeneity
3. Epigenetic Therapies and Clinical Implications
3.1. DNA Methylation Inhibitors
3.2. Histone Deacetylase Inhibitors
3.3. Histone Methyltransferase and Demethylase Inhibitors
3.4. Bromodomain and Extra-Terminal Domain (BET) Inhibitors
3.5. Non-Coding RNA-Based Therapies
3.5.1. MicroRNA-Based Therapies
3.5.2. LncRNAs, circRNAs and eRNAs as Therapeutic Targets
3.5.3. CRISPR/dCas9 Epigenome Editing
3.5.4. siRNAs and snoRNAs
3.6. Epigenetic Modulation of the Bone Microenvironment by Tumor-Derived Factors
3.7. Chromatin Remodeling and Its Role in Cancer Progression and Bone Metastasis
Drug | Class | Cancer Type/Indication | Status | Clinical Trial Phase/Approval | Reference |
---|---|---|---|---|---|
5-Azacytidine | DNMT inhibitor | MDS, AML, brain metastasis | FDA-approved | Approved | [166,175] |
Decitabine | DNMT inhibitor | MDS, AML, bone metastasis | FDA-approved | Approved | [173] |
Guadecitabine (SGI-110) | SGI—Second-generation DNMT inhibitor | Advanced solid tumors | In trials | Phase I | [176] |
GSK3685032 | DNMT selective inhibitor | AML | Preclinical | Preclinical | [177] |
Vorinostat | HDAC inhibitor | Cutaneous T-cell lymphoma | FDA-approved | Approved | [267] |
Romidepsin | HDAC inhibitor | Peripheral T-cell lymphoma | FDA-approved | Approved | [183] |
Panobinostat | HDAC inhibitor | Multiple myeloma | FDA-approved | Approved | [268] |
Belinostat | HDAC inhibitor | Peripheral T-cell lymphoma | FDA-Approved | Approved | [184] |
Entinostat | HDAC inhibitor | Breast cancer | In trials | Breakthrough therapy | [185] |
Mocetinostat | HDAC inhibitor | Solid tumors | In trials | Phase I/II | [182] |
Givinostat | HDAC inhibitor | Polycythemia vera, leukemia | In trials | Phase III | [187] |
Abexinostat | HDAC inhibitor | Lymphoma, solid tumors | In trials | Phase II | [188] |
Tubastatin A | HDAC6 inhibitor | Preclinical cancers | Preclinical | Preclinical | [84] |
PCI-34051 | HDAC8 inhibitor | Specific cancers | Preclinical | Preclinical | [190] |
REC-2282 (AR-42) | HDAC inhibitor | Neurofibromatosis type 2, meningioma | In trials | Phase I/II | [186] |
Tazemetostat | EZH2 inhibitor | Follicular lymphoma, epithelioid sarcoma | FDA-approved | Approved | [198] |
GSK126 | EZH2 inhibitor | Solid tumors | Preclinical | Preclinical | [196] |
ORY-1001 | KDM1A inhibitor | AML, breast cancer | Preclinical | Preclinical | [201] |
Tan IIA | KDM1A natural inhibitor | Breast cancer | Preclinical | Preclinical | [201] |
JQ1 | BET inhibitor | Breast cancer bone metastasis | Preclinical | Preclinical | [210] |
Molibresib | BET inhibitor | NUT midline carcinoma | In trials | Phase I | [206] |
Birabresib (OTX015) | BET inhibitor | NHL, AML | In trials | Phase Ib | [207] |
RO6870810 | BET inhibitor | DLBCL, solid tumors | In trials | Phase I/II | [209] |
BI 894999 | BET inhibitor | DLBCL, solid tumors | In trials | Phase Ia/Ib | [203] |
Pelabresib (CPI0610) | BET inhibitor | Myelofibrosis | In trials | Phase II/III | [211] |
MRX34 | miR-34a mimic (RNA-based therapy) | Liver cancer, melanoma | Terminated | Phase I (terminated) | [220] |
MRG-106 (Cobomarsen) | Antagomir (miR-155) | Cutaneous T-cell lymphoma | In trials | Phase I | [222,223] |
siG12D- LODER | siRNA | Pancreatic cancer | In trials | Phase I/II | [242] |
FHD-286 | BRG1/BRM dual ATPase inhibitor | AML, SWI/SNF-mutant cancers | In trials | Phase I | [254] |
4. Future Direction
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Zhra, M.; Holail, J.H.; Mohammad, K.S. Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies. Pharmaceuticals 2025, 18, 1140. https://doi.org/10.3390/ph18081140
Zhra M, Holail JH, Mohammad KS. Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies. Pharmaceuticals. 2025; 18(8):1140. https://doi.org/10.3390/ph18081140
Chicago/Turabian StyleZhra, Mahmoud, Jasmine Hanafy Holail, and Khalid S. Mohammad. 2025. "Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies" Pharmaceuticals 18, no. 8: 1140. https://doi.org/10.3390/ph18081140
APA StyleZhra, M., Holail, J. H., & Mohammad, K. S. (2025). Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies. Pharmaceuticals, 18(8), 1140. https://doi.org/10.3390/ph18081140