Paradigms for Precision Medicine in Epichaperome Cancer Therapy.
Animals
Antineoplastic Agents
/ administration & dosage
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 Imaging
Neoplasms
/ diagnostic imaging
Precision Medicine
/ methods
Protein Interaction Mapping
/ methods
Protein Interaction Maps
/ drug effects
Theranostic Nanomedicine
/ methods
Xenograft Model Antitumor Assays
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
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
11 11 2019
11 11 2019
Historique:
received:
27
02
2019
revised:
20
08
2019
accepted:
23
09
2019
pubmed:
2
11
2019
medline:
28
5
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31668946
pii: S1535-6108(19)30427-1
doi: 10.1016/j.ccell.2019.09.007
pmc: PMC6996250
mid: NIHMS1545075
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Molecular Chaperones
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
559-573.e7Subventions
Organisme : NIA NIH HHS
ID : R56 AG061869
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232130
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155226
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA158609
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA192937
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032969
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172546
Pays : United States
Organisme : NCI NIH HHS
ID : R24 CA083084
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA186866
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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