Chaperome heterogeneity and its implications for cancer study and treatment

J Biol Chem. 2019 Feb 8;294(6):2162-2179. doi: 10.1074/jbc.REV118.002811. Epub 2018 Nov 8.


The chaperome is the collection of proteins in the cell that carry out molecular chaperoning functions. Changes in the interaction strength between chaperome proteins lead to an assembly that is functionally and structurally distinct from each constituent member. In this review, we discuss the epichaperome, the cellular network that forms when the chaperome components of distinct chaperome machineries come together as stable, functionally integrated, multimeric complexes. In tumors, maintenance of the epichaperome network is vital for tumor survival, rendering them vulnerable to therapeutic interventions that target critical epichaperome network components. We discuss how the epichaperome empowers an approach for precision medicine cancer trials where a new target, biomarker, and relevant drug candidates can be correlated and integrated. We introduce chemical biology methods to investigate the heterogeneity of the chaperome in a given cellular context. Lastly, we discuss how ligand-protein binding kinetics are more appropriate than equilibrium binding parameters to characterize and unravel chaperome targeting in cancer and to gauge the selectivity of ligands for specific tumor-associated chaperome pools.

Keywords: 70 kilodalton heat shock protein (Hsp70); biomarker; cancer biology; cancer therapy; chaperome; chaperone; chemical biology; chemical probes; epichaperome; heat shock protein 90 (Hsp90); protein networks; stress response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / therapeutic use
  • Drug Delivery Systems / methods*
  • Humans
  • Molecular Chaperones* / antagonists & inhibitors
  • Molecular Chaperones* / metabolism
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Protein Interaction Maps / drug effects*


  • Antineoplastic Agents
  • Molecular Chaperones
  • Neoplasm Proteins