Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors
Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors
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DOI：
10.1007/978-1-4939-7477-1_29
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发表时间：
2018-01-01
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影响因子：
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通讯作者：
Trepel, Jane B.
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作者：
Yuno, Akira;Lee, Min-Jung;Trepel, Jane B.
分子伴侣热休克蛋白90 （Hsp90）抑制剂自1998年以来一直作为抗癌药物在临床开发中。目前已经有18种Hsp90抑制剂（Hsp90i）进入临床，尽管它们的结构不同，但都靶向伴侣蛋白n端与atp结合的Bergerat折叠。目前，有5种Hsp90抑制剂处于临床试验阶段，该类药物尚未获批。开发临床有效的Hsp90抑制剂的一个障碍是，共同开发这类药物固有抗癌活性的预测性或药效学标记物的临床试验比例非常低。在这里，我们提供了Hsp90抑制剂的临床发展概况，回顾了过去使用的药效学分析，并重点介绍了Hsp90抑制剂临床开发的新方法。
Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have been in clinical development as anticancer agents since 1998. There have been 18 Hsp90 inhibitors (Hsp90i) that have entered the clinic, all of which, though structurally distinct, target the ATP-binding Bergerat fold of the chaperone N-terminus. Currently, there are five Hsp90 inhibitors in clinical trial and no approved drug in this class. One impediment to development of a clinically efficacious Hsp90 inhibitor has been the very low percentage of clinical trials that have codeveloped a predictive or pharmacodynamic marker of the anticancer activity inherent in this class of drugs. Here, we provide an overview of the clinical development of Hsp90 inhibitors, review the pharmacodynamic assays that have been employed in the past, and highlight new approaches to Hsp90 inhibitor clinical development.