Revisiting the role of antiandrogen strategies in ovarian cancer

Androgen 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

Physical activity and risk of ovarian cancer : Results from the Netherlands Cohort Study (The Netherlands)

Objective: To investigate the association between nonoccupational physical activity and the risk of ovarian cancer among post-menopausal women. Methods: The Netherlands Cohort Study on Diet and Cancer consists of 62,573 women aged 55-69 years at baseline. Information regarding baseline nonoccupational physical activity and history of sports activity was collected with a self-administered questionnaire in 1986. After 11.3 years of follow-up, 252 cases of invasive epithelial ovarian cancer were available for case-cohort analysis. Results: In multivariate analysis and compared to women who spent less than 30 min per day on physical activity, the rate ratios (RRs) of ovarian cancer for women who spent up to 60, 90 and >90 min per day were 0.78, 0.86 and 0.72, respectively (95% confidence interval (CI) for the top category, 0.48-1.06; p-trend, 0.15). Women who spent more than 2 h per week on recreational biking and walking had a reduced risk of ovarian cancer (RR = 0.65; 95% CI: 0.41-1.01) compared to women who never participated in recreational biking or walking. Conclusions: These data suggest a modest inverse association between moderate physical activity and ovarian cancer risk. Vigorous physical activity was not associated with ovarian cancer risk. © Springer-Verlag 2006

Androgen receptor protein levels are significantly reduced in serous ovarian carcinomas compared with benign or borderline disease but are not altered by cancer stage or metastatic progression

The androgen receptor (AR) is expressed in a majority of ovarian carcinomas, but its role in disease development remains unclear. In this study, AR and a novel AR molecular chaperone called small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) were investigated to assess their potential role in ovarian carcinogenesis. First, an AR and SGTA-positive ovarian cancer cell line was identified to examine whether SGTA influenced AR subcellular localization. Next, relative protein levels of AR and SGTA were measured in two sets of clinical samples: (1) 46 serous ovarian carcinomas (stages I-IV), 9 serous borderline tumors, and 11 benign ovarian tumors; and (2) 24 patient-matched stage III primary and metastatic serous ovarian tumors. Ablation of SGTA protein in OVCAR3 cells significantly increased AR nuclear localization under basal (p ≤ 0.001) and androgen-stimulated (p ≤ 0.001) conditions. In the first clinical set, AR levels were significantly lower in early- (I/II) and late-stage (III/IV) cancers compared with benign (p ≤ 0.001) but not borderline ovarian tumors. SGTA alone did not discriminate between groups but the AR/SGTA ratio was significantly lower in carcinomas and borderline tumors compared with benign tumors (p ≤ 0.001 and 0.015, respectively). In the second clinical set, matched primary and metastatic serous ovarian cancers did not significantly differ for any parameter measured. Collectively, our results suggest that SGTA can influence AR signaling in ovarian cancer cells and that AR signaling capacity may be reduced with the development but not metastatic progression of serous ovarian cancer.Miriam S. Butler, Carmela Ricciardelli, Wayne D. Tilley, Theresa E. Hicke