Synapse - Paradigms for precision medicine in epichaperome cancer therapy

Paradigms for precision medicine in epichaperome cancer therapy Journal Article

Authors:	Pillarsetty, N.; Jhaveri, K.; Taldone, T.; Caldas-Lopes, E.; Punzalan, B.; Joshi, S.; Bolaender, A.; Uddin, M. M.; Rodina, A.; Yan, P.; Ku, A.; Ku, T.; Shah, S. K.; Lyashchenko, S.; Burnazi, E.; Wang, T.; Lecomte, N.; Janjigian, Y.; Younes, A.; Batlevi, C. W.; Guzman, M. L.; Roboz, G. J.; Koziorowski, J.; Zanzonico, P.; Alpaugh, M. L.; Corben, A.; Modi, S.; Norton, L.; Larson, S. M.; Lewis, J. S.; Chiosis, G.; Gerecitano, J. F.; Dunphy, M. P. S.
Article Title:	Paradigms for precision medicine in epichaperome cancer therapy
Abstract:	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. © 2019 Elsevier Inc. Pillarsetty et al. demonstrate the ability to visualize the epichaperome, a pathologic protein-protein interaction network, and to measure inhibitor engagement from mice and patients at single-tumor resolution in real time, which facilitates the optimization of dose and schedule selection. © 2019 Elsevier Inc.
Keywords:	unclassified drug; nonhuman; positron emission tomography; protein protein interaction; in vitro study; drug development; cancer therapy; biological activity; isotope labeling; biomarker; radiopharmaceutical agent; pu h71; heat shock protein 90; drug tumor level; protein inhibitor; personalized medicine; chaperone; liquid chromatography-mass spectrometry; human; priority journal; article; precision medicine; ic50; epichaperome; theranostic nanomedicine; higher-order protein assembly; hyperconnected protein networks; kinetic selectivity; pet imaging for precision oncology; pharmacometrics; pu-h71 companion diagnostic; pu h71 i 124; mda-mb-468 cell line; therapeutic dose
Journal Title:	Cancer Cell
Volume:	36
Issue:	5
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2019-11-11
Start Page:	559
End Page:	573.e7
Language:	English
DOI:	10.1016/j.ccell.2019.09.007
PUBMED:	31668946
PROVIDER:	scopus
PMCID:	PMC6996250
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074398844&doi=10.1016%2fj.ccell.2019.09.007&partnerID=40&md5=c4b517c851569723e5e7bd0d8c1af15c
Notes:	Source: Scopus