Revisiting the Role of Antiandrogen Strategies in Ovarian Cancer

Abstract

After completing this course, the reader will be able to:1. Explain the role of the androgen axis in the development of ovarian cancer.2. Discuss the potential compounds with anti-androgen activity that can be assessed for the treatment of patients with ovarian cancer.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTAndrogen receptors are frequently expressed in epithelial ovarian cancer (EOC). Their role in the development of EOC is not fully understood. In the present review we first discuss the epidemiological data linking a hyperandrogen state to a higher risk for ovarian cancer, second describe in vitro studies of the role of androgens in influencing the growth of EOC, and finally review the completed clinical trials with compounds that exploit the androgen axis in patients with ovarian cancer. The therapeutic approaches that inhibit androgen signaling have so far produced only modest response rates. In the light of new data regarding the role of androgen stimulation in the evolution of EOC and the emergence of new compounds used for the treatment of other hormone-driven malignancies, such as prostate and breast cancer, we provide suggestions for new studies of antiandrogen therapeutics in the treatment of EOC. A specific example is the new agent abiraterone. In addition, we propose a panel of molecules that could be assessed as potential biomarkers that may aid patient selection for this approach in the future. The Oncologist

A magic drug target: Androgen receptor

“…AR overexpression is observed in a majority of human ovarian cancers, and a large number of evidence indicates that androgen/AR signaling stimulates proliferation, migration, and invasion of ovarian cancer cells. 19,[116][117][118][119] The proliferation promoted by androgen and AR signaling is achieved mainly via interaction with a number of key elements including cell cycle regulators, TGF-β pathway, IL-6/IL-8, epidermal growth factor receptor, telomerase, and AR coactivators. 19 However, AR is consistently the key part in the signaling pathway.…”

The role of the androgen receptor in ovarian cancer carcinogenesis and its clinical implications

“…Taken together, this data suggests that anti-androgen in ovarian cancer may have certain effects under viable application conditions [12]. However, clinical trials testing anti-androgen therapy in ovarian cancer to date are relatively small and nonrandomized.…”

A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth

“…Taken together, these results suggest a role for AR antagonists in the treatment of ovarian cancer. The fact that Hey-A8 cells are more sensitive to AR modulators on plastic than on the omental microenvironment, suggest that the omentum might downregulate AR in tumor cells and might help explain why therapeutic approaches that inhibit androgen signaling have so far produced only modest response rates in clinic 33 . Furthermore, it has been reported by Scully et al 34 that ovarian metastases from gastrointestinal tract carcinomas had stroma that were found neither in the primary gastrointestinal tumor nor in the extra ovarian metastasis and contained lutenized, steroidogenic ovarian stromal cells.…”