Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5α-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis.

中文翻译：

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肾上腺衍生的雄激素在去势抵抗性前列腺癌中的作用。

尽管雄激素剥夺治疗（晚期转移性前列腺癌的治疗的第一线）后，去势抵抗性前列腺癌（CRPC）仍然具有雄激素依赖性，尽管循环睾丸激素的去势水平较高。CRPC的特征是类固醇生成酶的表达水平发生变化，使肿瘤能够从循环的肾上腺雄激素前体中衍生出强效雄激素。肿瘤内雄激素的生物合成导致了规范性雄激素（如5α-二氢睾丸激素（DHT））和特征性较差的11-氧化雄激素的局部生产，直到最近在CRPC的背景下，这种现象仍被忽视。在这篇综述中，我们讨论了规范性和11-氧化雄激素前体对CRPC中肿瘤内雄激素库的贡献。我们目前的证据表明，CRPC仍然是雄激素依赖性的，并讨论了类固醇生成酶表达的变化以及这些变化如何影响肿瘤内雄激素生物合成的各种途径。最后，我们总结了针对肾上腺衍生雄激素生物合成的当前治疗策略。