Epigenetic therapy for ovarian cancer: promise and progress

Clinical Epigenetics

卷:11

Alejandro Villagra¹  Sara Moufarrij²  Aneil Srivastava²  Elisa Arthofer²  Monica Dandapani²  Stephanie Gomez²  Katherine B. Chiappinelli²  Micael Lopez-Acevedo³ 

[1] Department of Biochemistry & Molecular Medicine, The George Washington University;

[2] Department of Microbiology, Immunology, & Tropical Medicine, The George Washington University;

[3] Department of Obstetrics & Gynecology, The George Washington University;

关键词: Ovarian cancer;    Epigenetics;    DNA methylation;    Histone modifications;    DNMT inhibitors;    HDAC inhibitors;   

DOI  :  10.1186/s13148-018-0602-0

来源: DOAJ

【 摘 要 】

Abstract Ovarian cancer is the deadliest gynecologic malignancy, with a 5-year survival rate of approximately 47%, a number that has remained constant over the past two decades. Early diagnosis improves survival, but unfortunately only 15% of ovarian cancers are diagnosed at an early or localized stage. Most ovarian cancers are epithelial in origin and treatment prioritizes surgery and cytoreduction followed by cytotoxic platinum and taxane chemotherapy. While most tumors will initially respond to this treatment, recurrence is likely to occur within a median of 16 months for patients who present with advanced stage disease. New treatment options separate from traditional chemotherapy that take advantage of advances in understanding of the pathophysiology of ovarian cancer are needed to improve outcomes. Recent work has shown that mutations in genes encoding epigenetic regulators are mutated in ovarian cancer, driving tumorigenesis and resistance to treatment. Several of these epigenetic modifiers have emerged as promising drug targets for ovarian cancer therapy. In this article, we delineate epigenetic abnormalities in ovarian cancer, discuss key scientific advances using epigenetic therapies in preclinical ovarian cancer models, and review ongoing clinical trials utilizing epigenetic therapies in ovarian cancer.

【 授权许可】

Unknown