Epigenetics as a mechanism driving polygenic clinical drug resistance

Glasspool, R.M., Teodoridis, J.M. and Brown, R. (2006) Epigenetics as a mechanism driving polygenic clinical drug resistance. British Journal of Cancer, 94(8), pp. 1087-1092. (doi: 10.1038/sj.bjc.6603024)

Abstract

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance.

• Item Type: Articles
• Keywords: chemotherapy; biomarkers; DNA methylation; drug resistance; epigenetics
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Brown, Prof Robert and Teodoridis, Dr Jens
• Authors: Glasspool, R.M., Teodoridis, J.M., and Brown, R.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: British Journal of Cancer
• Publisher: Nature Publishing Group
• ISSN: 1532-1827
• Copyright Holders: Copyright © 2006 Nature Publishing Group
• First Published: First published in British Journal of Cancer 94(8):1087-1092
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher