The Clinical Development of Histone Deacetylase Inhibitors As Targeted Anticancer Drugs

Overview

Journal Expert Opin Investig Drugs

Specialty Pharmacology

Date 2010 Aug 7

PMID 20687783

Citations 120

Authors

Paul A Marks

Affiliations

Soon will be listed here.

Abstract

Importance Of The Field: Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs.

Area Covered In This Review: This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death.

What The Reader Will Gain: There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not completely understood. It is clear that these different HDACs are not redundant in their activity. This review focuses on the mechanisms by which HDAC inhibitors can induce transformed cell growth arrest and cell death, inhibit cell mobility and have antiangiogenesis activity. There are more than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides and fatty acids, in various stages of clinical trials and many more compounds in preclinical development. The chemically different HDAC inhibitors may target different HDACs.

Take Home Message: There are extensive preclinical studies with transformed cells in culture and tumor-bearing animal models, as well as limited clinical studies reported to date, which indicate that HDAC inhibitors will be most useful when used in combination with cytotoxic or other targeted anticancer agents.

Citing Articles

Histone deacetylase inhibitors: targeting epigenetic regulation in the treatment of acute leukemia.

Xiao T, Chen Z, Xie Y, Yang C, Wu J, Gao L Ther Adv Hematol. 2024; 15:20406207241283277.

PMID: 39421716 PMC: 11483798. DOI: 10.1177/20406207241283277.

Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer.

Bajpai P, Agarwal S, Afaq F, Al Diffalha S, Chandrashekar D, Kim H J Exp Clin Cancer Res. 2024; 43(1):192.

PMID: 38992681 PMC: 11238352. DOI: 10.1186/s13046-024-03106-8.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Dai L, Zhang C, Gao W, Pan J, Huang S, Zhang Y Transl Cancer Res. 2024; 13(5):2372-2386.

PMID: 38881946 PMC: 11170521. DOI: 10.21037/tcr-23-2169.

Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator.

Karati D, Mukherjee S, Roy S Med Oncol. 2024; 41(4):84.

PMID: 38438564 DOI: 10.1007/s12032-024-02303-x.

TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication .

Yin J, Wang S, Ren S, Liang Z, Ge J, Sun Y Front Microbiol. 2023; 14:1284439.

PMID: 38107853 PMC: 10722228. DOI: 10.3389/fmicb.2023.1284439.

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