Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer.
Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer.
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DOI：
10.1515/bc.2010.044
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发表时间：
2010-04
影响因子：
3.7
通讯作者：
Denmeade SR
中科院分区：
文献类型：
--
作者：
LeBeau AM;Kostova M;Craik CS;Denmeade SR
前列腺特异性抗原（PSA）或激肽释放酶相关肽酶3（KLK 3）作为前列腺癌的生物标志物的作用是众所周知的;然而，其丝氨酸蛋白酶活性在前列腺癌中的确切生理作用仍然是一个谜。PSA在雄激素依赖性和非依赖性前列腺癌中都以高水平产生。研究表明，骨和软组织转移灶周围环境中存在高水平的活性PSA。这一证据，加上越来越多的实验证据，表明PSA在前列腺癌的病理生物学中起着重要作用。这些观察结果支持PSA选择性抑制剂作为前列腺癌靶向治疗和成像的有用工具的发展。在这里，我们回顾了迄今为止在开发PSA选择性抑制剂方面进行的研究。不同的方法来确定PSA底物特异性和创建抑制剂进行了讨论。此外，PSA独特的活性位点特征以及这些基序如何帮助我们开发PSA靶向药物的研究也得到了强调。
The role of prostate-specific antigen (PSA) or kallkirein-related peptidase 3 (KLK3) as a biomarker for prostate cancer is well known; however, the precise physiologic role of its serine protease activity in prostate cancer remains a mystery. PSA is produced at high levels by both androgen-dependent and -independent prostate cancers. Studies have documented high levels of active PSA in the milieu surrounding osseous and soft tissue metastases. This evidence, coupled with growing experimental evidence, suggests that PSA plays an important role in the pathobiology of prostate cancer. These observations support the development of PSA-selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer. Here we review the research that has been conducted to date on developing selective inhibitors for PSA. The different approaches used to determine PSA substrate specificity and for creating inhibitors is discussed. In addition, the unique active site characteristics of PSA and how these motifs aided our research in developing PSA targeted agents is highlighted.