Innovative approaches to the clinical development of DNA methylation inhibitors as epigenetic remodeling drugs - PubMed (original) (raw)

Review

Innovative approaches to the clinical development of DNA methylation inhibitors as epigenetic remodeling drugs

Anthony J Murgo. Semin Oncol. 2005 Oct.

Abstract

The most extensively studied inhibitors of DNA methylation are the cytidine analogs 5-azacytidine (5-aza-CR; azacitidine) and 5-aza-2'- deoxycytidine (5-aza-CdR; decitabine). Despite decades of nonclinical and clinical research, there remains considerable interest in finding innovative and better ways to use these DNA methyltransferase (DNMT) inhibitors. A mounting body of data supports the role of methylation in silencing genes involved in tumor growth and resistance. This information has fueled further nonclinical and clinical research on ways to use inhibitors of methylation to restore normal gene expression and function. As such, recent clinical strategies have shifted from simply evaluating cytotoxic effects to exploring and optimizing the ability of these agents to restore or reactivate gene expression and putative targets. This article considers innovative approaches to develop and evaluate inhibitors of DNA methylation as epigenetic remodeling agents for the treatment of cancer. These include optimization of dose and schedule, restoration or enhancement of sensitivity to other treatment modalities, and combinations with other agents including histone deacetylase inhibitors.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources