Paradigms for Precision Medicine in Epichaperome Cancer Therapy

Cancer Cell. 2019 Nov 11;36(5):559-573.e7. doi: 10.1016/j.ccell.2019.09.007. Epub 2019 Oct 24.


Alterations in protein-protein interaction networks are at the core of malignant transformation but have yet to be translated into appropriate diagnostic tools. We make use of the kinetic selectivity properties of an imaging probe to visualize and measure the epichaperome, a pathologic protein-protein interaction network. We are able to assay and image epichaperome networks in cancer and their engagement by inhibitor in patients' tumors at single-lesion resolution in real time, and demonstrate that quantitative evaluation at the level of individual tumors can be used to optimize dose and schedule selection. We thus provide preclinical and clinical evidence in the use of this theranostic platform for precision medicine targeting of the aberrant properties of protein networks.

Keywords: PET imaging for precision oncology; PU-H71 companion diagnostic; biomarker; cancer therapy; epichaperome; higher-order protein assembly; hyperconnected protein networks; kinetic selectivity; pharmacometrics; precision medicine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Molecular Chaperones / antagonists & inhibitors*
  • Molecular Chaperones / metabolism
  • Molecular Imaging
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Precision Medicine / methods
  • Protein Interaction Mapping / methods
  • Protein Interaction Maps / drug effects*
  • Protein Interaction Maps / genetics
  • Theranostic Nanomedicine / methods
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Molecular Chaperones