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<p>Epigenetic dysregulation has been identified as a key hallmark of cancer. Histone acetylation is a major factor in regulating tumour formation among these alterations. Acetylation of histone is balanced by the coordination between the HDACs and HATs enzymes. HDACs remove an acetyl group from the histone, leading to chromatin condensation and aiding in oncogenesis. Studies have established HDACIs as potential therapeutics for the treatment of various malignancies. Therefore, the pharmacokinetics and pharmacodynamics of HDACIs need a thorough understanding. HDACIs have been approved for tackling haematological malignancies, but their role in solid tumours as monotherapeutic agents is questionable. In this review, we have discussed the functions of HDACs in tumourigenesis. Additionally, we attempt to deliver a thorough analysis of the HDACIs under clinical trials and address the synergistic effect of combination therapies with FDA-approved drugs to overcome the limitations of monotherapy, offering a novel perspective on improving cancer treatment outcomes.</p>

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Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment

  • 期刊论文

  • 发表日期：

    2025年7月13日

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  • Api Talom,
  • Ankurika Barhoi,
  • Taba Jirpu,
  • Bikram Dawn,
  • Arnab Ghosh

摘要

Epigenetic dysregulation has been identified as a key hallmark of cancer. Histone acetylation is a major factor in regulating tumour formation among these alterations. Acetylation of histone is balanced by the coordination between the HDACs and HATs enzymes. HDACs remove an acetyl group from the histone, leading to chromatin condensation and aiding in oncogenesis. Studies have established HDACIs as potential therapeutics for the treatment of various malignancies. Therefore, the pharmacokinetics and pharmacodynamics of HDACIs need a thorough understanding. HDACIs have been approved for tackling haematological malignancies, but their role in solid tumours as monotherapeutic agents is questionable. In this review, we have discussed the functions of HDACs in tumourigenesis. Additionally, we attempt to deliver a thorough analysis of the HDACIs under clinical trials and address the synergistic effect of combination therapies with FDA-approved drugs to overcome the limitations of monotherapy, offering a novel perspective on improving cancer treatment outcomes.