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Published on: August 10, 2017
Recent Advancements in the Development of HDAC/Tubulin Dual-Targeting Inhibitors
Christine Tran1, Abdallah Hamze1
1BioCIS, CNRS (Centre National de Recherche Scientifique), Université Paris-Saclay, 91400 Orsay, France.
Abstract:
Histone deacetylases (HDACs) have become one of the main targets in cancer therapy due to their involvement in various biological processes, including gene regulation, cell proliferation, and differentiation. Microtubules, as key elements of the cell cytoskeleton, also represent important therapeutic targets in anticancer drugs research. These proteins are involved in diverse cellular functions, especially mitosis, cell signaling, and intracellular trafficking. With the emergence of multi-target therapy during the last decades, the combination of HDAC and tubulin inhibitors has been envisioned as a practical approach for optimizing the therapeutic efficacy of antitumor molecules. HDAC/tubulin dual-targeting inhibitors offer the advantages of the synergistic action of both compounds, along with a significant decrease in their respective toxicities and drug resistance. This review will detail the major recent advancements in the development of HDAC/tubulin dual inhibitors over the last decade and their impact on anticancer drugs discovery.
Insights
Dual-targeting inhibitors combining histone deacetylase (HDAC) and tubulin inhibition show promise for cancer therapy. This approach enhances efficacy and reduces toxicity and resistance in anticancer drug development.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylases (HDACs) regulate gene expression, cell proliferation, and differentiation, making them key cancer targets.
- Microtubules, crucial for cell structure and function, are also vital targets in anticancer drug research.
- Multi-target therapy offers a strategy to enhance antitumor efficacy and overcome drug resistance.
Purpose of the Study:
- To review recent advancements in dual-targeting inhibitors of HDACs and tubulin.
- To explore the impact of these dual inhibitors on anticancer drug discovery.
- To highlight the benefits of combining HDAC and tubulin inhibition.
Main Methods:
- Literature review of recent studies (last decade) on HDAC/tubulin dual inhibitors.
- Analysis of the synergistic effects and reduced toxicities of dual-targeting agents.
- Evaluation of the impact on anticancer drug discovery and development.
Main Results:
- Development of novel HDAC/tubulin dual inhibitors has progressed significantly.
- These dual inhibitors demonstrate synergistic anticancer activity.
- Combined inhibition leads to decreased toxicity and drug resistance compared to single-target agents.
Conclusions:
- HDAC/tubulin dual-targeting inhibitors represent a promising strategy in cancer therapy.
- This approach optimizes therapeutic efficacy and minimizes adverse effects.
- Further research into these dual inhibitors is crucial for advancing anticancer drug discovery.
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