McSweeney Sean, Bergom Hannah E, Prizment Anna, Halabi Susan, Sharifi Nima, Ryan Charles, Hwang Justin
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, USA.
Endocr Oncol. 2022 Jun 7;2(1):R51-R64. doi: 10.1530/EO-22-0058. eCollection 2022 Jan.
The androgen receptor (AR) signaling pathway regulates the progression of prostate cancer (PC). Metastatic castration-resistant prostate cancer (mCRPC) patients generally receive AR-targeted therapies (ART) or androgen-deprivation therapies (ADT) with the initial response; however, resistance is inevitably observed. Prior studies have shown activity and upregulation of a family of androgen production, uptake, and conversion - APUC genes - based on genomic analyses of patient germlines. Genetic variants of some APUC genes, such as the conversion gene, HSD3B1, predict response to second-generation androgen-targeted therapies. Studies have begun to elucidate the overall role of APUC genes, each with unique actionable enzymatic activity, in mCRPC patient outcomes. The current role and knowledge of the genetic and genomic features of APUC genes in advanced prostate cancer and beyond are discussed in this review. These studies inform of how interpreting behavior of APUC genes through genomic tools will impact the treatment of advanced prostate cancer.
雄激素受体（AR）信号通路调节前列腺癌（PC）的进展。转移性去势抵抗性前列腺癌（mCRPC）患者通常接受雄激素靶向治疗（ART）或雄激素剥夺治疗（ADT），并会有初始反应；然而，不可避免地会出现耐药性。先前的研究基于对患者种系的基因组分析，显示了一组雄激素产生、摄取和转化基因——APUC基因的活性和上调。一些APUC基因的遗传变异，如转化基因HSD3B1，可预测对第二代雄激素靶向治疗的反应。研究已开始阐明具有独特可操作酶活性的APUC基因在mCRPC患者预后中的整体作用。本综述讨论了APUC基因的遗传和基因组特征在晚期前列腺癌及其他方面的当前作用和相关知识。这些研究说明了通过基因组工具解读APUC基因的行为将如何影响晚期前列腺癌的治疗。
