Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention
Аутори
Ružić, DušanĐoković, Nemanja
Srdić-Rajić, Tatjana
Echeverria, Cesar
Nikolić, Katarina
Santibanez, Juan F.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accord...ingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.
Кључне речи:
HDAC inhibitors / PROTAC / bifunctional inhibitors / cancer / chemoprevention / clinical trials / dietary-derived inhibitors / epigenetic / histone deacetylasesИзвор:
Pharmaceutics, 2022, 14, 1, 209-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200015 (Универзитет у Београду, Институт за медицинска истраживања) (RS-MESTD-inst-2020-200015)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Ružić, Dušan AU - Đoković, Nemanja AU - Srdić-Rajić, Tatjana AU - Echeverria, Cesar AU - Nikolić, Katarina AU - Santibanez, Juan F. PY - 2022 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1212 AB - The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies. T2 - Pharmaceutics T1 - Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention IS - 1 SP - 209 VL - 14 DO - 10.3390/pharmaceutics14010209 ER -
@article{ author = "Ružić, Dušan and Đoković, Nemanja and Srdić-Rajić, Tatjana and Echeverria, Cesar and Nikolić, Katarina and Santibanez, Juan F.", year = "2022", abstract = "The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.", journal = "Pharmaceutics", title = "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention", number = "1", pages = "209", volume = "14", doi = "10.3390/pharmaceutics14010209" }
Ružić, D., Đoković, N., Srdić-Rajić, T., Echeverria, C., Nikolić, K.,& Santibanez, J. F.. (2022). Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics, 14(1), 209. https://doi.org/10.3390/pharmaceutics14010209
Ružić D, Đoković N, Srdić-Rajić T, Echeverria C, Nikolić K, Santibanez JF. Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics. 2022;14(1):209. doi:10.3390/pharmaceutics14010209 .
Ružić, Dušan, Đoković, Nemanja, Srdić-Rajić, Tatjana, Echeverria, Cesar, Nikolić, Katarina, Santibanez, Juan F., "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention" in Pharmaceutics, 14, no. 1 (2022):209, https://doi.org/10.3390/pharmaceutics14010209 . .