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This version published online on July 2, 2009
Endocrinology, doi:10.1210/en.2009-0404
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Submitted on March 31, 2009
Accepted on June 23, 2009

Epigenetic Changes in Ovarian Cancer

Curt Balch, Fang Fang, Daniela E. Matei, Tim H-M. Huang, and Kenneth P. Nephew*

Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47405; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN 46202; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202; Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; The Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210; Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, 46202

* To whom correspondence should be addressed. E-mail: knephew{at}indiana.edu.

Epigenetic aberrations, including DNA methylation, histone modifications, and microRNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, associated with distinct disease subtypes, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic modifications are potentially reversible by epigenetic therapies, including inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic monotherapies have not shown activity against solid tumors, including ovarian cancer, preclinical studies suggest they will be effective when used in combination with one another or with conventional chemotherapeutics, and combinatorial epigenetic therapy regiments are being examined in cancer clinical trials. A greater understanding of the role of epigenetics in ovarian neoplasia will provide for improved interventions against this devastating malignancy.


Key words: epigenetics • ovarian cancer • platinum resistance • DNMT inhibitor • chemosensitization







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