Histone Deacetylase (HDAC) Inhibitors: A Promising Weapon to Tackle Therapy Resistance in Melanoma

Melanoma is an aggressive malignant tumor, arising more commonly on the skin, while it can also occur on mucosal surfaces and the uveal tract of the eye. In the context of the unresectable and metastatic cases that account for the vast majority of melanoma-related deaths, the currently available the...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-03, Vol.23 (7), p.3660
Main Authors: Palamaris, Kostas, Moutafi, Myrto, Gakiopoulou, Hariklia, Theocharis, Stamatios
Format: Article
Language:English
Subjects:
Clinical trials
Deacetylation
DNA methylation
Drug resistance
Epigenetics
HDAC inhibitors
Histone deacetylase
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylase Inhibitors - therapeutic use
Histone Deacetylases
Histones
Humans
Immunotherapy
in vitro
Inhibitors
Melanoma
Melanoma - drug therapy
Melanoma - pathology
Metastases
Molecular biology
Mucosa
mucosal melanoma
Mutation
Review
therapy resistance
Tumors
uveal melanoma
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Summary:Melanoma is an aggressive malignant tumor, arising more commonly on the skin, while it can also occur on mucosal surfaces and the uveal tract of the eye. In the context of the unresectable and metastatic cases that account for the vast majority of melanoma-related deaths, the currently available therapeutic options are of limited value. The exponentially increasing knowledge in the field of molecular biology has identified epigenetic reprogramming and more specifically histone deacetylation (HDAC), as a crucial regulator of melanoma progression and as a key driver in the emergence of drug resistance. A variety of HDAC inhibitors (HDACi) have been developed and evaluated in multiple solid and hematologic malignancies, showing promising results. In melanoma, various experimental models have elucidated a critical role of histone deacetylases in disease pathogenesis. They could, therefore, represent a promising novel therapeutic approach for advanced disease. A number of clinical trials assessing the efficacy of HDACi have already been completed, while a few more are in progress. Despite some early promising signs, a lot of work is required in the field of clinical studies, and larger patient cohorts are needed in order for more valid conclusions to be extracted, regarding the potential of HDACi as mainstream treatment options for melanoma.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23073660