A Chemical Biology Approach to the Chaperome in Cancer-HSP90 and Beyond. Review uri icon

Overview

abstract

  • 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.

publication date

  • April 1, 2020

Research

keywords

  • Gene Expression Regulation, Neoplastic
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Neoplasms

Identity

PubMed Central ID

  • PMC6773535

Scopus Document Identifier

  • 85069716423

Digital Object Identifier (DOI)

  • 10.1007/s12192-017-0776-y

PubMed ID

  • 30936118

Additional Document Info

volume

  • 12

issue

  • 4