Rudolfsson Stina Häggström, Bergh Anders
Umeå University, Surgical and Perioperative Sciences, Urology and Andrology, NUS, bld 6M, 2 floor Umeå 90185, Sweden.
Expert Opin Ther Targets. 2009 Feb;13(2):219-25. doi: 10.1517/14728220802626249.
Hypoxia is common in prostate tumours, promoting tumour progression and impairing treatment responses. Hypoxia stimulates angiogenesis but blood vessels formed in tumours are functionally abnormal so the tissue remains hypoxic. Castration treatment is the standard therapy for advanced prostate cancer. In non-malignant prostate tissue castration-induced epithelial cell death is in part mediated by vascular insult and acute hypoxia, but in prostate tumours the cell death response is less prominent and the tumours will eventually relapse. The effect of androgen ablation therapy should therefore be enhanced by additional targeting of the vasculature and hypoxic tumour cells. However if castration fails to kill a sufficiently large number of cells it could by inducing hypoxia make the situation worse. Androgen ablation treatment, may, after the initial vascular insult, result in temporary vascular normalisation and transiently increased tissue oxygen levels. During this time window, which needs to be better defined, the efficacy of cytotoxic drug and radiation treatments are probably enhanced. In order to allow development of more effective treatment strategies for advanced prostate cancer we need to understand the role of hypoxia in prostate cancer progression and treatment responses. With this knowledge we can properly tailor and time additional treatments with androgen ablation.
缺氧在前列腺肿瘤中很常见，它促进肿瘤进展并损害治疗反应。缺氧刺激血管生成，但肿瘤中形成的血管功能异常，因此组织仍处于缺氧状态。去势治疗是晚期前列腺癌的标准疗法。在非恶性前列腺组织中，去势诱导的上皮细胞死亡部分由血管损伤和急性缺氧介导，但在前列腺肿瘤中，细胞死亡反应不那么明显，肿瘤最终会复发。因此，通过额外靶向脉管系统和缺氧肿瘤细胞，可以增强雄激素剥夺疗法的效果。然而，如果去势不能杀死足够数量的细胞，它可能会通过诱导缺氧使情况变得更糟。雄激素剥夺治疗在最初的血管损伤后，可能会导致暂时的血管正常化和组织氧水平短暂升高。在这个需要更好界定的时间窗内，细胞毒性药物和放射治疗的疗效可能会增强。为了开发更有效的晚期前列腺癌治疗策略，我们需要了解缺氧在前列腺癌进展和治疗反应中的作用。有了这些知识，我们就可以合理地调整雄激素剥夺的额外治疗并确定其时间。
