Abstract：
Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.
摘要：
雄激素受体信号传导对于前列腺癌治疗抵抗的发展至关重要。在类固醇生成酶中，3β-羟基类固醇脱氢酶（3βHSD）在性腺外雄激素合成中起关键作用，特别是3βHSD1。与原发性前列腺肿瘤相比，在去势抵抗的前列腺癌肿瘤中观察到3βHSD的表达增加，表明他们参与了阉割抵抗。最近的研究将3βHSD1与对雄激素受体信号传导抑制剂的抗性联系起来。3βHSD1表达的调控涉及多种因素,包括转录因子，微环境影响，和转录后修饰。此外,HSD3B1基因型的临床意义，特别是rs1047303变体已经被广泛研究。HSD3B1基因型对治疗结果的影响因治疗而异，提示HSD3B1基因分型在个性化医疗中的潜力。靶向3βHSD可能是前列腺癌治疗的有希望的策略。总的来说,了解3βHSD的作用及其遗传变异可能有助于前列腺癌新疗法的开发和优化。
