Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochaperones, and other cofactors. Changes in the expression levels of components of the chaperome, in the interaction strength among chaperome components, alterations in chaperome constituency, and in the cellular location of chaperome members, are all hallmarks of cancer. Here we aim to provide an overview on how chemical biology has played a role in deciphering such complexity in the biology of the chaperome in cancer and in other diseases. The focus here is narrow and on pathologic changes in the chaperome executed by enhancing the interaction strength between components of distinct chaperome pathways, specifically between those of HSP90 and HSP70 pathways. We will review chemical tools and chemical probe-based assays, with a focus on HSP90. We will discuss how kinetic binding, not classical equilibrium binding, is most appropriate in the development of drugs and probes for the chaperome in disease. We will then present our view on how chaperome inhibitors may become potential drugs and diagnostics in cancer.

中文翻译：

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癌症 HSP90 及其他分子伴侣的化学生物学方法。

癌症通常与伴侣的改变有关，伴侣是伴侣、共伴侣和其他辅助因子的集合。分子伴侣表达水平的变化、分子伴侣成分之间相互作用强度的变化、分子伴侣组成的改变以及分子伴侣成员的细胞位置的变化，都是癌症的标志。在这里，我们的目的是概述化学生物学如何在破译癌症和其他疾病中伴侣组生物学的复杂性方面发挥作用。这里的重点是狭窄的，通过增强不同伴侣通路组分之间的相互作用强度，特别是 HSP90 和 HSP70 通路之间的相互作用强度，来执行伴侣组的病理变化。我们将回顾化学工具和基于化学探针的测定，重点关注 HSP90。我们将讨论动力学结合（而不是经典平衡结合）如何最适合开发疾病中分子伴侣的药物和探针。然后，我们将提出关于伴侣抑制剂如何成为癌症潜在药物和诊断方法的观点。