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a Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA; b Division of Medical Oncology B, Regina Elena Cancer Institute, Rome, Italy; c Department of Human Pathology and Oncology, Laboratory of Biomedical Technology and Oncology, Siena, Italy
Key Words. Breast cancer • Gene expression regulation • Estrogen receptors • Anticancer drug combinations
Correspondence: Antonio Giordano, M.D., Ph.D., Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, BioLife Sciences Bldg. 333, Temple University, 1900 North 12th Street, Philadelphia, Pennsylvania 19122-6009, USA. Telephone: 215-204-9520; Fax: 215-204-9522; e-mail: giordano{at}temple.edu
In industrialized countries, breast cancer is the most common tumor in women. The tumor expression of estrogen receptors (ERs) is a very important marker for prognosis and a marker that is predictive of response to endocrine therapy. The loss of ER expression portends a poor prognosis and, in a significant fraction of breast cancers, this repression is a result of the hypermethylation of CpG islands within the ER-
promoter. Hypermethylation is one of the best known epigenetic events in mammalian cells. Over the last few years, many studies have found that other epigenetic events, such as deacetylation and methylation of histones, are involved in the complex mechanism that regulates promoter transcription. The exact interplay of these factors in transcriptional repression activity is not yet well understood. Inhibitors of some of these are currently being studied as new drugs able to restore ER- protein expression in ER-–negative breast cancer cells and to promote apoptosis and differentiation. Demethylating agents and histone deacetylase (HDAC) inhibitors are candidates for becoming potent new drugs in cancer therapy. This paper reviews the current understanding of the role of epigenetic information in the development of cancer and its significance in breast cancer as predictive markers of ER status and as new targets of anticancer therapy.
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