Isoform-Selective HDAC Inhibitors May Improve Efficacy and Offer Reduced Adverse Effects Compared With Pan-HDAC Inhibitors

 HDAC inhibitors are a class of compounds that inhibit histone deacetylases, a class of enzymes that remove acetyl groups from an amino acid on a histone. The term originates from the fact that these inhibitors were first identified as enzymes that function to remove acetyl groups from lysine residues on the N-terminal tails of histones. The inhibitors can be structurally classified into at least four classes: hydrox-amates, cyclic peptides, aliphatic acids and ben-zamides.

HDAC inhibitors significantly impact several biological processes including development, proliferation, differentiation, and cell death. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. HDACs also play significant role in gene expression, especially in prostate, gastric, lung, esophageal, colon, and breast cancers.

High prevalence of cancer is expected to boost demand for HDAC inhibitors in Germany, Mexico, Japan and rest of the world. For instance, according to the World Health Organization’s Globocan 2018, Germany recorded 608,742 cases of cancer 247,462 cancer-related deaths in 2018. HDAC inhibitors can also be used in combination with other inhibitors for the treatment of relapsed refractory Hodgkin lymphoma. For instance, in November 2020, researchers from The University of Texas MD Anderson Cancer Center, U.S., reported that combined histone deacetylase and mTOR inhibition has salutary activity in patients with relapsed refractory Hodgkin lymphoma.

The adoption of HDAC inhibitors is limited due to the fact that there is insufficient understanding of the molecular mechanisms underlying the response to histone deacetylase inhibitors in cancer patients. Although the targets and mechanisms of action of these inhibitors is not fully understood, they have significant potential in cancer treatment. Isoform-selective HDAC inhibitors may improve efficacy and offer reduced adverse effects compared with pan-HDAC inhibitors. These inhibitors can be used in combination with other therapies to enhance clinical outcomes of various diseases.