More evidence intratumoral DHT synthesis drives castration-resistant prostate cancer

• 来源期刊: 亚洲男性学杂志（英文版）
• 年，卷（期）: 2014,（1）
• 页码范围: 99-100
• 页数: 2页
• 语种: 英文
• DOI: 10.4103/1008-682X.122200

摘要

Again-of-function stabilizing somatic mutation in 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1,HSD3B1) was reported in castration-resistant prostate cancer.The A→C nucleotide polymorphism replaced asparagine-367 with threonine (3βHSD1-N367T) as a homozygous somatic mutation in a subset of castration-resistant prostate cancers by loss of heterozygosity of the wild-type allde.Increased stability of3βHSD 1-N367T was associated with decreased ubiquitin-mediated degradation and higher levels of dihydrotestosterone (DHT).The studies suggest that genetic instability in castration-resistant prostate cancer favors the more stable 3βHSD 1-N367T mutant that contributes to drug resistance.A somatic mutation in a steroid metabolic enzyme required for DHT synthesis provides further support for intratumoral androgen synthesis contributing to prostate cancer progression. It has been known for ＞60years that growth of prostate cancer depends on testicular androgen.Prostate cancers undergo remission for 1-2years following androgen deprivation therapy,but recur in the absence of testicular androgen.