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Advances of HDAC dual inhibitors in breast cancer treatment
Chuanjiang Wu1, Jiyong Wu2, Linlin Ni3
1College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.
Abstract:
Breast cancer remains the most common prevalent malignancy among women globally, constituting the primary cause of cancer-associated mortality. While therapeutic advancements have been achieved, persistent challenges in treatment resistance, disease recurrence, and distant metastasis continue to undermine clinical outcomes. Histone deacetylases (HDACs), a conserved family of epigenetic regulators, catalyze the removal of acetyl groups from histone substrates, thereby orchestrating chromatin remodeling and transcriptional regulation. Beyond their canonical epigenetic functions, these enzymes critically modulate diverse oncogenic progresses, including cell proliferation, differentiation, and metastasis, positioning them as promising therapeutic targets in oncology. Recent studies have demonstrated the therapeutic prospects of dual-target inhibitors. Current evidence suggests such combinatorial approaches not only enhance anti-neoplastic efficacy through multi-modal mechanisms but also circumvent the drug resistance frequently observed in single-target therapy. This therapeutic paradigm shift underscores the clinical potential of HDAC-based dual inhibitors for breast cancer management. In this review, we systematically analyze recent advancements in dual-target HDAC inhibitors (HDACis), integrating mechanistic insights, preclinical evidences, and translational implications to establish a foundational framework for future therapeutic development and clinical implementation.
Insights
Dual-target histone deacetylase inhibitors (HDACis) show promise for overcoming breast cancer treatment resistance and metastasis. This review explores their mechanisms and potential for improved patient outcomes.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Breast cancer is a leading cause of mortality in women, with treatment resistance and metastasis posing significant challenges.
- Histone deacetylases (HDACs) are epigenetic regulators involved in cancer progression, making them potential therapeutic targets.
- Single-target therapies face limitations due to drug resistance.
Purpose of the Study:
- To review advancements in dual-target histone deacetylase inhibitors (HDACis) for breast cancer.
- To analyze their mechanisms of action, preclinical evidence, and translational potential.
- To provide a framework for future development and clinical application of these inhibitors.
Main Methods:
- Systematic review of recent literature on dual-target HDAC inhibitors.
- Analysis of mechanistic insights into their anti-cancer effects.
- Evaluation of preclinical data and translational implications.
Main Results:
- Dual-target HDAC inhibitors offer enhanced anti-neoplastic efficacy through multi-modal mechanisms.
- These combinatorial approaches can circumvent drug resistance observed with single-target therapies.
- Recent studies demonstrate significant therapeutic prospects for dual-target HDAC inhibitors in preclinical models.
Conclusions:
- Dual-target HDAC inhibitors represent a promising therapeutic strategy for breast cancer management.
- Further research and clinical implementation are warranted to leverage their full potential.
- This approach may overcome current limitations in breast cancer treatment, including resistance and recurrence.
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