Murez T, Basset V, Audenet F, Lebret T, Branchereau J
Service d'urologie et transplantation rénale, hôpital Lapeyronie, CHU de Montpellier, 371 avenue du Doyen-Gaston-Giraud, 34295 Montpellier Cedex 5, France.
Prog Urol. 2013 Oct;23 Suppl 1:S1-8. doi: 10.1016/S1166-7087(13)70040-X.
Despite initial sensitivity to androgen deprivation, most metastatic prostate cancer patients will experience recurrence or progression. This evolution, which occurs while seric testosterone level is low, is called castration resistant prostate cancer (CRPC).
MEDLINE database was requested for French or English articles published until September 2012 responding to the following keywords: "castration resistant", "prostatic neoplasms", "androgens", "testosterone", "regulat*". Here is a summary of relevant data concerning both qualitative and quantitative hormonal regulation.
androgen blood testing is not related to tissue concentrations, as prostate cancer cells exhibit higher hormones levels. Despite its higher biological efficiency, dihydrotestosterone is not the only mediator of androgen-dependent transcription. Androgen synthesis implies many pathways including lot of alternative ones. Steroïdogenesis can occur out of the testicles and the adrenals, and maybe in tumor cell or tissue. Major and minor androgens levels, as those of co-repressors and activators inside the tumor cell leads to a smooth androgen activity modulation. Many drugs have the ability to block those different steps.
Castration resistance reflects an androgen activity in tumor cells while major androgen pathway activators are lowered. Alternate pathway include steroids pumps, de novo synthesis by tumor cells or their environment, minor androgens activation by co-factors regulation. Many drugs are known to inhibit those escaping ways. Nowadays they are not efficient enough, because of other minor pathways becoming dominant. Investigations are required but would need new detection techniques of low androgen concentrations in blood as in tissues.
尽管大多数转移性前列腺癌患者最初对雄激素剥夺治疗敏感，但仍会出现复发或进展。这种在血清睾酮水平较低时发生的进展被称为去势抵抗性前列腺癌（CRPC）。
检索MEDLINE数据库，查找截至2012年9月发表的法语或英语文章，检索关键词如下：“去势抵抗”、“前列腺肿瘤”、“雄激素”、“睾酮”、“调节*”。以下是关于定性和定量激素调节的相关数据总结。
雄激素血液检测与组织浓度无关，因为前列腺癌细胞中的激素水平更高。尽管双氢睾酮具有更高的生物学活性，但它并非雄激素依赖性转录的唯一介质。雄激素合成涉及许多途径，包括许多替代途径。类固醇生成可发生在睾丸和肾上腺之外，也可能发生在肿瘤细胞或组织中。肿瘤细胞内主要和次要雄激素水平以及共抑制因子和激活因子的水平导致雄激素活性的平稳调节。许多药物有能力阻断这些不同步骤。
去势抵抗反映了肿瘤细胞中的雄激素活性，而主要雄激素途径激活剂水平降低。替代途径包括类固醇泵、肿瘤细胞或其周围环境的从头合成、通过辅因子调节激活次要雄激素。已知许多药物可抑制这些逃逸途径。目前它们的效果不够理想，因为其他次要途径变得占主导地位。需要进行研究，但这需要新的血液和组织中低雄激素浓度检测技术。
