Hormone response in ovarian cancer: time to reconsider as a clinical target?

Abstract

Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence from in vitro studies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response.

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

“…Ovarian cancer is a common disease among women, and is said to be connected to reproductive disorders, age, and hormone) (Merritt and Cramer, 2010;Modugno et al, 2012 (Westin et al, 2013;Coleman et al, 2013).…”

Evidence of androgen action in endometrial and ovarian cancers

“…A large Swedish study has reported that women who were admitted to hospital for ovarian cysts before the age of 29 were at increased risk of ovarian cancer later in life (Borgfeldt & Andolf 2004). Ovarian cancer risk is consistently reported as being reduced by factors that interrupt ovulation, including use of oral contraceptives, pregnancy or breastfeeding (Modugno et al 2012) as well as tubal ligation with the latter most closely associated with endometrioid tumours (Rice et al 2013). Pooled data from 12 prospective cohort studies in North America and Europe identified 2000 ovarian epithelial cancers in approximately half a million women.…”

“…In their 2012 review of the epidemiological evidence that androgens might play a role in development of epithelial ovarian cancers, Modugno et al argued that although some epidemiological evidence supported a role for androgens in development of disease, there were also studies that did not support this assertion (reviewed in Modugno et al (2012)). …”

“…There have been a number of studies showing overexpression of AR in ovarian cancer with papers also reporting the impact of androgens on gene expression and survival of ovarian cancer cell lines (reviewed in Modugno et al (2012)). In a recent study, positive AR immunostaining was reported in two sets of ovarian cancer tissues.…”

“…Some studies on androgen action in ovarian carcinomas may need to be treated with caution as some of the established cell lines may not be of ovarian cancer origin (Korch et al 2012). In a recent review, Modugno et al (2012) summarised the evidence that therapies targeting ARs for treatment of women with ovarian cancer might be a promising strategy. They highlighted the small scale of most trials; they had used anti-androgens for treatment of women with recurrent cancer and variable results were obtained.…”