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Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Drug Combinations with HDAC Inhibitors in Antitumor Therapy
Noemi Arrighetti1, Cristina Corno1, Laura Gatti1
1Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract:
The treatment of tumor cells with HDAC inhibitors (HDACi) induces a range of effects including apoptosis, cell cycle arrest, differentiation and senescence, modulation of immune response, and altered angiogenesis. The single-agent activities of several HDACi have been tested in preclinical and clinical studies and are currently the subject of ongoing clinical trials. Although HDACi have been shown to be effective as a single agent against a defined subset of hematological tumors, less convincing results have been found in the treatment of solid tumors. Since current clinical trials of single-agent HDACi showed limited efficacy, in this review we focus on drug combinations including HDACi with conventional chemotherapeutic agents and novel targeted agents. Particular emphasis has been devoted to combinations effective in solid tumors and to combinations between HDACi and immunotherapies. An outline of novel combination strategies, including a new generation of more potent and specific HDACi (e.g., compounds with adamantine and noradamantane as scaffolds) as well as chemical hybrid molecules, has been provided. The paradoxical role of HDACs as tumor suppressors in developing tumors and as therapeutic targets in established neoplasms has also been considered.
Insights
Histone deacetylase inhibitors (HDACi) show promise in treating hematological tumors but have limited efficacy in solid tumors. Combining HDACi with other therapies, including immunotherapies, offers a promising strategy for solid tumor treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylase inhibitors (HDACi) induce various anti-tumor effects like apoptosis and cell cycle arrest.
- While effective in some hematological cancers, single-agent HDACi efficacy is limited in solid tumors.
Purpose of the Study:
- To review drug combinations involving HDAC inhibitors for cancer treatment, focusing on solid tumors.
- To explore novel combination strategies, including with targeted agents and immunotherapies.
Main Methods:
- Review of preclinical and clinical studies on HDAC inhibitor monotherapy and combination therapies.
- Emphasis on combinations demonstrating efficacy in solid tumors and with immunotherapies.
Main Results:
- HDACi show significant potential when combined with conventional chemotherapy and targeted agents.
- Combinations of HDACi with immunotherapies represent a promising area for solid tumor treatment.
- Novel HDACi generations and chemical hybrid molecules are being developed for enhanced specificity and potency.
Conclusions:
- Combination therapies are crucial for maximizing the therapeutic potential of HDAC inhibitors, especially in solid tumors.
- Future research should focus on novel HDACi and combination strategies, including immunotherapy, to overcome limitations of single-agent treatments.
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