Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Faculty of Medicine, Benha University, Benha, Egypt.
JCI Insight. 2019 Oct 3;4(19):129715. doi: 10.1172/jci.insight.129715.
Clinical trials of high-dose androgen (HDA) therapy for prostate cancer (PC) have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of HDAs, we applied an unbiased integrative approach using genetic screens and transcriptional profiling of PC cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both HDA and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors that are amenable to HDA therapy.
雄激素（HDA）治疗前列腺癌（PC）的临床试验显示出有希望的疗效，但由于缺乏识别可能的应答者的标准而受到限制。为了阐明控制 HDAs 生长抑制作用的因素，我们应用了一种无偏的综合方法，对具有或不具有雄激素介导的生长抑制表型敏感性的 PC 细胞进行遗传筛选和转录谱分析。通过这项全面的分析，我们确定了决定对 HDA 和雄激素撤退反应的遗传事件和相关信号网络。我们将这些发现应用于开发一个基因特征，该特征可能作为治疗反应的早期指标，并识别对 HDA 治疗有反应的肿瘤的男性。
