Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression.
Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume.
We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01).
Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.British Journal of Cancer advance online publication, 2 March 2017; doi:10.1038/bjc.2017.42 www.bjcancer.com.
British journal of cancer. 2017 Mar 02 [Epub ahead of print]
Geun Taek Lee, Christopher S Han, Young Suk Kwon, Rutveej Patel, Parth K Modi, Seok Joo Kwon, Izak Faiena, Neal Patel, Eric A Singer, Han-Jong Ahn, Wun-Jae Kim, Isaac Y Kim
Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA., Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA., Department of Urology, Asan Medical Center, Seoul 05505, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.