Chemoresistance in human ovarian cancer: the role of apoptotic regulators
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BioMed Central
Open Access
Review
Chemoresistance in human ovarian cancer: the role of apoptotic regulators Michael Fraser1, Brendan Leung1, Arezu Jahani-Asl1, Xiaojuan Yan1, Winston E Thompson2 and Benjamin K Tsang*1 Address: 1Department of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa, Ottawa Health Research Institute, Ottawa, Canada K1Y 4E9, Canada and 2Department of Obstetrics & Gynecology and Cooperative Reproductive Science Research Center, Morehouse School of Medicine, Atlanta, GA 30310, USA Email: Michael Fraser - [email protected]; Brendan Leung - [email protected]; Arezu Jahani-Asl - [email protected]; Xiaojuan Yan - [email protected]; Winston E Thompson - [email protected]; Benjamin K Tsang* - [email protected] * Corresponding author
Published: 07 October 2003 Reproductive Biology and Endocrinology 2003, 1:66
Received: 26 June 2003 Accepted: 07 October 2003
This article is available from: http://www.RBEj.com/content/1/1/66 © 2003 Fraser et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Recent evidence suggests that deregulation of key pro- and anti-apoptotic pathways is a key factor in the onset and maintenance of chemoresistance. Furthermore, the discovery of novel interactions between these pathways suggests that chemoresistance may be multi-factorial. Ultimately, the decision of the cancer cell to live or die in response to a chemotherapeutic agent is a consequence of the overall apoptotic capacity of that cell. In this review, we discuss the biochemical pathways believed to promote cell survival and how they modulate chemosensitivity. We then conclude with some new research directions by which the fundamental mechanisms of chemoresistance can be elucidated.
Ovarian Cancer and Chemoresistance: A Molecular and Cellular Perspective Although ovarian cancer ranks seventh among all cancers in women in terms of prevalence, almost 60% of those who have ovarian cancer eventually succumb to the disease. In 2002, 23,300 new cases were identified and 13,900 deaths were reported in the United States alone. While breast cancer has a much higher incidence (203,500 new cases), it has a considerably lower mortality rate (39,600 deaths; approximately 20% mortality rate) when compared to that of ovarian cancer [1]. In fact, ovarian cancer causes more deaths than any other cancer of the female reproductive system. Much of the failure to obtain better cure rates in ovarian cancer is a consequence of late diagnosis; only about 25% of patients are diagnosed when the disease is still confined to the ovary. At
advanced stages (stages III and IV), when the disease has spread beyond the ovary, treatment becomes increasingly ine
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