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Minireview: Epigenetic Changes in Ovarian Cancer

Medical Sciences (C.B., F.F., K.P.N.), School of Medicine, Indiana University, Bloomington, Indiana 47405; Melvin and Bren Simon Cancer Center (C.B., D.E.M., K.P.N.), Departments of Cellular and Integrative Physiology (C.B., K.P.N.) and Obstetrics and Gynecology (K.P.N.), and Division of Hematology/Oncology (D.E.M., K.P.N.), Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202; and The Human Cancer Genetics Program (T.H.-M.H.), Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210

Address all correspondence and requests for reprints to: Professor Kenneth P. Nephew, Medical Sciences, Indiana University School of Medicine, 302 Jordan Hall, 1001 East 3rd Street, Bloomington, Indiana 47405-4401. E-mail: knephew{at}indiana.edu.

Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA 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.