Drug insight: Histone deacetylase inhibitors--development of the new targeted anticancer agent suberoylanilide hydroxamic acid.

Publication/Presentation Date

3-1-2005

Abstract

This review focuses on the discovery and development of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA). Post-translational modifications of the histones of chromatin are important factors in regulating gene expression--so-called epigenetic gene regulation. Acetylation and deacetylation of lysine residues in histone tails, controlled by the activities of HDACs and histone acetyltransferases, are among the most studied post-translational modification of histones. In addition to chromatin protein, transcription factors, cell-signaling regulatory proteins, and proteins regulating cell death are substrates of HDACs and may be altered in function by HDAC inhibitors. HDAC inhibitors have several remarkable aspects. For instance, despite HDACs being ubiquitously distributed through chromatin, SAHA selectively alters the transcription of relatively few genes, and normal cells are at least 10-fold more resistant than transformed cells to SAHA and related HDAC inhibitor-induced cell death. HDAC inhibitors represent a relatively new group of targeted anticancer compounds, which are showing significant promise as agents with activity against a broad spectrum of neoplasms, at doses that are well tolerated by cancer patients. SAHA is one of the HDAC inhibitors most advanced in development. It is in phase I and II clinical trials for patients with both hematologic and solid tumors.

Volume

2

Issue

3

First Page

150

Last Page

157

ISSN

1743-4254

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

16264908

Department(s)

Administration and Leadership

Document Type

Article

Link to Full Text

Share

COinS