1. ¹Molecular Radiation Biology, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia
2. ²Epigenetics in Human Health and Disease, Baker Medical Research Institute, The Alfred Medical Research and Education Precinct, Prahran, Vic, Australia

Correspondence: Dr A El-Osta, The Alfred Medical Research and Education Precinct (AMREP), Baker Medical Research Institute, Epigenetics in Human Health and Disease Laboratory, Second Floor, Commercial Road, Prahran, Vic 3181, Australia. E-mail: assam.el-osta@baker.edu.au

Received 11 November 2005; Revised 19 December 2005; Accepted 20 December 2005; Published online 6 February 2006.

Abstract

Histone deacetylase (HDAC) inhibitors are emerging as a new class of targeted cancer chemotherapeutics. Several HDAC inhibitors are currently in clinical trials and promising anticancer effects at well-tolerated doses have been observed for both hematologic and solid cancers. HDAC inhibitors have been shown to induce cell-cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. However, it is known that these compounds induce varying responses in different cells and biological settings, and identifying their precise mechanisms of action is an area of great interest. Important findings are continually expanding our understanding of the cellular effects of HDAC inhibitors and recent studies will be briefly outlined in this review. In addition to their intrinsic anticancer properties, numerous studies have demonstrated that HDAC inhibitors can modulate cellular responses to other cytotoxic modalities including ionizing radiation, ultraviolet radiation and chemotherapeutic drugs. Hence, there is a growing interest in potential clinical use of HDAC inhibitors in combination with conventional cancer therapies. In this review, the interaction of HDAC inhibitors with other anticancer agents is discussed. The focus of the article is on the different mechanisms by which HDAC inhibitors enhance the sensitivity of cells to the effects of ionizing radiation.