1. Paradigms for Precision Medicine in Epichaperome Cancer Therapy
- Author
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Blesida Punzalan, Monica L. Guzman, Gabriela Chiosis, Nagavarakishore Pillarsetty, Nicolas Lecomte, Thomas Ku, Connie W. Batlevi, Jason S. Lewis, Mary L. Alpaugh, Larry Norton, Alexander Bolaender, Jacek Koziorowski, Anas Younes, Eva Burnazi, Komal Jhaveri, Anna Rodina, Mohammad M. Uddin, Gail J. Roboz, Suhasini Joshi, Smit K. Shah, Tai Wang, Mark Dunphy, Anson Ku, Pengrong Yan, Pat Zanzonico, Adriana D. Corben, Yelena Y. Janjigian, Shanu Modi, Tony Taldone, Eloisi Caldas-Lopes, Steven M. Larson, Serge K. Lyashchenko, and John F. Gerecitano
- Subjects
0301 basic medicine ,Cancer Research ,Proteome ,Computer science ,Cancer therapy ,Antineoplastic Agents ,Computational biology ,Article ,Drug Administration Schedule ,Theranostic Nanomedicine ,Malignant transformation ,Epigenesis, Genetic ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Interaction network ,Cell Line, Tumor ,Neoplasms ,Protein Interaction Mapping ,medicine ,Animals ,Humans ,HSP90 Heat-Shock Proteins ,Protein Interaction Maps ,Precision Medicine ,Dose-Response Relationship, Drug ,Cancer ,Cell Biology ,medicine.disease ,Precision medicine ,Xenograft Model Antitumor Assays ,Pharmacometrics ,Biomarker (cell) ,Molecular Imaging ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,Protein network ,Biomarkers ,Molecular Chaperones - 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.
- Published
- 2019