Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Histone deacetylase inhibitors (HDACi) exhibit significant anticancer activity, especially in hematological malignancies.
• The precise mechanisms underlying HDACi clinical efficacy, whether direct cytotoxicity or immune modulation, remain under investigation.

Purpose of the Study:

• To provide an overview of the mechanisms of HDACi activity.
• To highlight the role of HDACi in hematological malignancies and clinical trial observations.
• To focus on the immunomodulatory effects of HDACi.

Main Methods:

• Review of current scientific literature and clinical trial data.
• Analysis of molecular mechanisms of HDACi-induced apoptosis and cellular changes.
• Examination of HDACi effects on tumor immunogenicity and immune cell function.

Main Results:

• HDACi induce apoptosis via intrinsic and extrinsic pathways, proteasome system effects, reactive oxygen species production, and DNA damage.
• HDACi alter the tumor microenvironment and increase tumor cell immunogenicity.
• HDACi modulate cytokine signaling and T-cell polarization, potentially contributing to in vivo anti-cancer effects.

Conclusions:

• HDACi possess multifaceted anticancer mechanisms, including direct cytotoxic effects and immune system modulation.
• Understanding these mechanisms, particularly immune effects, is crucial for optimizing HDACi therapy in hematological cancers.
• Clinical observations support the broad activity of HDACi, warranting further investigation into their immunomodulatory potential.