| Literature DB >> 31668946 |
Nagavarakishore Pillarsetty1, Komal Jhaveri2, Tony Taldone3, Eloisi Caldas-Lopes3, Blesida Punzalan1, Suhasini Joshi3, Alexander Bolaender3, Mohammad M Uddin3, Anna Rodina3, Pengrong Yan3, Anson Ku1, Thomas Ku1, Smit K Shah3, Serge Lyashchenko4, Eva Burnazi4, Tai Wang3, Nicolas Lecomte5, Yelena Janjigian5, Anas Younes6, Connie W Batlevi6, Monica L Guzman7, Gail J Roboz7, Jacek Koziorowski1, Pat Zanzonico8, Mary L Alpaugh3, Adriana Corben9, Shanu Modi2, Larry Norton2, Steven M Larson10, Jason S Lewis10, Gabriela Chiosis11, John F Gerecitano6, Mark P S Dunphy12.
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.Entities:
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
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Year: 2019 PMID： 31668946 PMCID： PMC6996250 DOI： 10.1016/j.ccell.2019.09.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743