Targeting histone deacetylases for the treatment of cancer and inflammatory diseases.

Histone deacetylases (HDACs) are involved in chromatin remodeling and modification of nonhistone transcription regulatory proteins, thus modulating the expression of genes important for complex biological events. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation may be implicated in the pathogenesis of various diseases, including cancer and inflammatory diseases. A significant number of HDAC inhibitors (HDIs) have been developed in the past decade. These inhibitors demonstrate strong anti-neoplastic effects in vitro and in vivo by inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. More than a dozen HDIs are currently being evaluated in phase I-II clinical trials in patients with solid and hematological malignancies, and some have already shown promising activity with low toxicity. HDIs also exhibit strong anti-inflammatory effects in vitro and in animal models for various inflammatory diseases, thus representing a new class of promising agents for treating inflammatory diseases. This review provides an overview of HDACs in gene regulation, HDIs for cancer therapy and for potential treatment of inflammatory diseases, and future perspectives. (c) 2006 Wiley-Liss, Inc.