Abstract
Emerging evidence has suggested that androgen receptor signaling plays an important role in ovarian cancer outgrowth. Specifically, androgen receptor activation appears to be associated with increased risks of developing ovarian cancer and inducing tumor progression. However, conflicting findings have also been reported. This review summarizes and discusses the available data indicating the involvement of androgens as well as androgen receptor and related signals in ovarian carcinogenesis and cancer growth. Although the underlying molecular mechanisms for androgen receptor functions in ovarian cancer remain far from being fully understood, current observations may offer effective chemopreventive and therapeutic approaches, via modulation of androgen receptor activity, against ovarian cancer. Indeed, several clinical trials have been conducted to determine the efficacy of androgen deprivation therapy in patients with ovarian cancer.
Highlights
Ovarian cancer comprising a variety of histological subtypes is one of the most common types of gynecological malignancy, with an estimate of 295,414 new cases and 184,799 deaths occurring in 2018 worldwide [1]
AR signaling has been implicated in the pathogenesis and growth of malignancies, including prostate cancer for which androgen deprivation therapy remains the mainstay of management [2] and other types such as breast cancer [4] and bladder cancer [3]
In SKOV3 cells cultured in the absence of androgens, IL-6 and IL-8 were shown to induce their proliferation, which was completely blocked by specific neutralizing antibodies for IL-6/IL-8, as well as to up-regulate the expression and transcriptional activity of AR, which was not blocked by flutamide [72]
Summary
Ovarian cancer comprising a variety of histological subtypes is one of the most common types of gynecological malignancy, with an estimate of 295,414 new cases and 184,799 deaths occurring in 2018 worldwide [1]. It is often diagnosed at an advanced stage, presumably due to its asymptomatic characteristics, and still represents a deadly disease despite significant advances in treatment strategies. AR signaling has been implicated in the pathogenesis and growth of malignancies, including prostate cancer for which androgen deprivation therapy remains the mainstay of management [2] and other types such as breast cancer [4] and bladder cancer [3]. We review available data suggesting their modulation through the AR pathway and discuss underlying molecular mechanisms
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