Clinical studies of histone deacetylase inhibitors

Area of Science:

• Oncology
• Epigenetics
• Immunology

Background:

• Histone deacetylase inhibitors (HDACi) are a class of drugs that modulate gene expression through hyperacetylation of histone and nonhistone targets.
• Clinical trials have evaluated numerous HDACi over the past five years, revealing diverse effects on cancer cells, the tumor microenvironment, and immune system activity.

Purpose of the Study:

• This review focuses on the efficacy and safety of HDAC inhibitors in hematologic malignancies.
• To summarize the current understanding of HDAC inhibitor mechanisms and clinical outcomes in blood cancers.

Main Methods:

• Review of clinical trial data and scientific literature on HDAC inhibitors in hematologic malignancies.
• Analysis of reported toxicities and biomarker utility for HDAC inhibitor therapy.

Main Results:

• Single-agent HDAC inhibitors have demonstrated clinical responses primarily in advanced hematologic malignancies, including T-cell lymphoma, Hodgkin lymphoma, and myeloid malignancies.
• Common acute toxicities associated with HDAC inhibitors include fatigue, gastrointestinal issues, and transient cytopenias.
• Long-term toxicities remain largely unknown due to limited prolonged treatment data.

Conclusions:

• HDAC inhibitors are generally well-tolerated in the short term and show efficacy in specific hematologic cancers.
• Histone hyperacetylation serves as a biomarker for target engagement but does not reliably predict clinical response.
• The development of more predictive biomarkers is crucial for optimizing HDAC inhibitor therapy in oncology.