@article{e12d1dc5955a4490af4a0bcae7e2bba8,
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.",
author = "Nagavarakishore Pillarsetty and Komal Jhaveri and Tony Taldone and Eloisi Caldas-Lopes and Blesida Punzalan and Suhasini Joshi and Alexander Bolaender and Uddin, {Mohammad M.} and Anna Rodina and Pengrong Yan and Anson Ku and Thomas Ku and Shah, {Smit K.} and Serge Lyashchenko and Eva Burnazi and Tai Wang and Nicolas Lecomte and Yelena Janjigian and Anas Younes and Batlevi, {Connie W.} and Guzman, {Monica L.} and Roboz, {Gail J.} and Jacek Koziorowski and Pat Zanzonico and Alpaugh, {Mary L.} and Adriana Corben and Shanu Modi and Larry Norton and Larson, {Steven M.} and Lewis, {Jason S.} and Gabriela Chiosis and Gerecitano, {John F.} and Dunphy, {Mark P.S.}",
note = "Funding Information: This work was supported in part by the US NIH (R01 CA172546, R56 AG061869, R01 CA155226, P01 CA186866, P30 CA08748, R35 CA232130 and P50 CA192937), the Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Experimental Therapeutics Center of the Memorial Sloan Kettering Cancer Center, and Samus Therapeutics; T.W. is a Lymphoma Research Foundation fellow. Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Small-Animal Imaging Research Program grant no. R24 CA83084 and NIH Center grant no. P30 CA08748 are gratefully acknowledged. N.P. T.T. E.C.-L. B.P. S.J. A.B. M.M.U. E.D.G. A.R. P.Y. A.K. T.K. S.K.S. T.W. M.L.A. N.L. J.K. P.Z. and A.C. designed and performed the experiments. M.P.S.D. was principle investigator of the PU-PET clinical trial, J.F.G. and S.M. of the phase 1 dose-escalation clinical study, K.J. and S.M. of the phase 1b study in breast cancer, and G.J.R. of the single-patient AML study. S.L. and E.B. performed radiotracer synthesis for PU-PET. Y.J. A.Y. L.N. C.W.B. and M.L.G. provided the reagents. All authors participated in the design and analysis of various experiments and G.C. P.Z. T.T. S.M. J.S.L. S.M.L. J.F.G. and M.P.S.D. wrote the paper. Memorial Sloan Kettering Cancer Center holds the intellectual rights to PU-H71 and [124I]PU-H71 (PCT/US06/03,676, PCT/US2012/045861). Samus Therapeutics, of which G.C. and L.N. have partial ownership and are members of its scientific advisory board, has licensed PU-H71 and [124I]PU-H71. G.C. N.P. J.S.L. S.M.L. T.T. and M.L.A. are inventors on the licensed intellectual property. All other authors declare no competing interests. Funding Information: This work was supported in part by the US NIH ( R01 CA172546 , R56 AG061869 , R01 CA155226 , P01 CA186866 , P30 CA08748 , R35 CA232130 and P50 CA192937 ), the Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Experimental Therapeutics Center of the Memorial Sloan Kettering Cancer Center , and Samus Therapeutics ; T.W. is a Lymphoma Research Foundation fellow. Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Small-Animal Imaging Research Program grant no. R24 CA83084 and NIH Center grant no. P30 CA08748 are gratefully acknowledged. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = nov,
day = "11",
doi = "10.1016/j.ccell.2019.09.007",
language = "English (US)",
volume = "36",
pages = "559--573.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}