HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer
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ORIGINAL ARTICLE
HSD3B1 variant and androgen‑deprivation therapy outcome in prostate cancer Fei‑fei Han1 · Lu‑lu Ren1 · Ling‑ling Xuan1 · Ya‑li LV1 · He Liu1 · Li‑li Gong1 · Zhuo‑ling An1 · Li‑hong Liu1 Received: 21 July 2020 / Accepted: 20 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objective Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. Methods To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). Results Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39–2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48–0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. Conclusion The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer. Keywords Androgen-deprivation therapy · Prostate cancer · HSD3B1 · Gene variation
Introduction Androgen receptor (AR) was expressed in most of prostate cancers and the cancer growth is dependent upon androgen stimulation. The androgens supply of prostate cancer were gonadal testosterone and extra-gonadal androgens that mainly originate from the human adrenal but may also arise in part from de novo steroid-genesis from cholesterol within tumor [1]. The foundation therapy of metastatic prostate cancer comprises repressing testosterone production through Androgen-deprivation therapy (ADT) by medical or surgical * Fei‑fei Han [email protected] * Li‑hong Liu [email protected] 1
Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
castration which could inhibit gonadal androgen synthesis. ADT has raised overall survival (OS) for the past 70 years and gradually became the cornerstone of systemic therapy in prostate cancer [2]. Nevertheless, some castration sensitive prostate cancer will turn into castration-resista
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