Histone deacetylase inhibitors for leukemia treatment: current status and future directions

Abstract

Leukemia remains a major therapeutic challenge in clinical oncology. Despite significant advancements in treatment modalities, leukemia remains a significant cause of morbidity and mortality worldwide, as the current conventional therapies are accompanied by life-limiting adverse effects and a high risk of disease relapse. Histone deacetylase inhibitors have emerged as a promising group of antineoplastic agents due to their ability to modulate gene expression epigenetically. In this review, we explore these agents, their mechanisms of action, pharmacokinetics, safety and clinical efficacy, monotherapy and combination therapy strategies, and clinical challenges associated with histone deacetylase inhibitors in leukemia treatment, along with the latest evidence and ongoing studies in the field. In addition, we discuss future directions to optimize the therapeutic potential of these agents.

Keywords: Antineoplastic agents; Apoptosis; Epigenetics; HDAC inhibitor; Hematological malignancy; Histone deacetylases antagonist; Treatment resistance; Tumor microenvironment.

Fig. 1

HDAC inhibitors exhibit antileukemic effects, either as monotherapy or in combination with other treatment modalities