Prostate cancer-from steroid transformations to clinical translation

ChangK.-H.; SharifiN.

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Prostate cancer-from steroid transformations to clinical translation

机译：前列腺癌-从类固醇转化到临床翻译

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The survival benefit conferred by two hormonal agents in phase III trials has clinically validated the long suspected and now widely recognized phenomenon of castration-resistant prostate cancer (CRPC) hormone dependence. Abiraterone inhibits steroid 17-hydroxylase/17,20-lyase (CYP17A1) and blocks androgen synthesis, whereas enzalutamide directly binds and antagonizes the androgen receptor. Both agents are highly effective against CRPC and significantly prolong survival following docetaxel treatment. However, this clinical validation of the androgen pathway has led to questions regarding the fundamental mechanisms of CRPC, as well as resistance to abiraterone and enzalutamide. Our understanding of the predominant steroid transformation pathways that lead to dihydrotestosterone synthesis in CRPC is evolving. The role of steroidogenesis in the development of resistance to abiraterone and enzalutamide remains uncertain. The specific roles of candidate enzyme targets in the development of resistance to these agents must be defined if we are to identify novel targets for improved pharmacologic therapies.

机译：两种激素药物在III期临床试验中所获得的生存益处已在临床上证实了长期以来人们一直怀疑并现已广泛认可的去势抵抗性前列腺癌（CRPC）激素依赖性现象。阿比特龙抑制类固醇17-羟化酶/ 17,20-裂解酶（CYP17A1）并阻断雄激素合成，而enzalutamide直接结合并拮抗雄激素受体。两种药物对CRPC都非常有效，并在多西他赛治疗后显着延长了生存期。然而，这种雄激素途径的临床验证已经引起了关于CRPC的基本机制以及对阿比特龙和恩杂鲁胺的抗性的质疑。我们对导致CRPC中二氢睾丸激素合成的主要类固醇转化途径的理解正在发展。类固醇生成在对阿比特龙和恩杂鲁胺抗药性发展中的作用仍不确定。如果我们要确定用于改善药理疗法的新靶标，则必须定义候选酶靶标在对这些药物产生抗药性中的特定作用。

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《Nature reviews. Urology》 |2012年第12期|共4页
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ChangK.-H.; SharifiN.;
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中图分类泌尿科学（泌尿生殖系疾病）;
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1. Prostate cancer-from steroid transformations to clinical translation [J] . ChangK.-H., SharifiN. Nature reviews. Urology . 2012,第12期

机译：前列腺癌-从类固醇转化到临床翻译
2. Microbial transformations of steroids--XII. Progesterone hydroxylation profiles are modulated by post-translational modification of an electron transfer protein in Streptomyces roseochromogenes. [J] . Berrie JR, Williams RA, Smith KE The Journal of Steroid Biochemistry and Molecular Biology . 2001,第1期

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4. Digital Transformation of Prostate Cancer Pathway and Optimizing Patient Experience, Patient Safety and Clinical Professionalism [C] . Joan Cahill, Ben Turney, Sean Wetherall, International Conference on Digital Human Modeling and Applications in Health, Safety, Ergonomics and Risk Management;International Conference on Human-Computer Interaction . 2019

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5. Co-expression of human kallikreins 2 and 3 in prostate and breast cancer: Clinical utility and mechanisms of steroid hormonal regulation. [D] . Magklara, Angeliki. 2003

机译：人激肽释放酶2和3在前列腺癌和乳腺癌中的共表达：类固醇激素调节的临床用途和机制。
6. University of Florida Clinical and Translational Science Institute: Transformation and Translation in Personalized Medicine [O] . David R. Nelson, Michael Conlon, Claire Baralt, 2011

机译：佛罗里达大学临床与转化科学研究所：个性化医学的转型与翻译
7. Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer [O] . Sagnik Sengupta, Mena Asha Krishnan, Sudeshna Chattopadhyay, 2019

机译：前列腺特异性膜抗原配体对前列腺癌诊断的临床翻译研究中的比较

Prostate cancer-from steroid transformations to clinical translation

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