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Townsend, E.C.* ; Murakami, M.A.* ; Christodoulou, A.N.* ; Christie, A.L.* ; Koster, J.* ; DeSouza, T.A.* ; Morgan, E.A.* ; Kallgren, S.P.* ; Liu, H.* ; Wu, S.C.* ; Plana, O.* ; Montero, J.* ; Stevenson, K.E.* ; Rao, P.* ; Vadhi, R.* ; Andreeff, M.* ; Armand, P.* ; Ballen, K.K.* ; Barzaghi-Rinaudo, P.* ; Cahill, S.* ; Clark, R.A.* ; Cooke, V.G.* ; Davids, M.S.* ; DeAngelo, D.J.* ; Dorfman, D.M.* ; Eaton, H.* ; Ebert, B.L.* ; Etchin, J.* ; Firestone, B.* ; Fisher, D.C.* ; Freedman, A.S.* ; Galinsky, I.A.* ; Gao, H.* ; Garcia, J.S.* ; Garnache-Ottou, F.* ; Graubert, T.A.* ; Gutierrez, A.* ; Halilovic, E.* ; Harris, M.H.* ; Herbert, Z.T.* ; Horwitz, S.M.* ; Inghirami, G.* ; Intlekoffer, A.M.* ; Ito, M.* ; Izraeli, S.* ; Jacobsen, E.D.* ; Jacobson, C.A.* ; Jeay, S.* ; Jeremias, I. ; Kelliher, M.A.* ; Koch, R.* ; Konopleva, M.* ; Kopp, N.* ; Kornblau, S.M.* ; Kung, A.L.* ; Kupper, T.S.* ; LaBoeuf, N.* ; LaCasce, A.S.* ; Lees, E.* ; Li, L.S.* ; Look, A.T.* ; Murakami, M.* ; Muschen, M.* ; Neuberg, D.* ; Ng, S.Y.* ; Odejide, O.O.* ; Orkin, S.H.* ; Paquette, R.R.* ; Place, A.E.* ; Roderick, J.E.* ; Ryan, J.A.* ; Sallan, S.E.* ; Shoji, B.* ; Silverman, L.B.* ; Soiffer, R.J.* ; Steensma, D.P.* ; Stegmaier, K.* ; Stone, R.M.* ; Tamburini, J.* ; Thorner, A.R.* ; van Hummelen, P.* ; Wadleigh, M.* ; Wiesmann, M.* ; Weng, A.P.* ; Wuerthner, J.U.* ; Williams, D.A.* ; Wollison, B.M.* ; Lane, A.A.* ; Letai, A.G.* ; Bertagnolli, M.M.* ; Ritz, J.* ; Brown, M.* ; Long, H.* ; Aster, J.C.* ; Shipp, M.A.* ; Griffin, J.D.* ; Weinstock, D.M.*

The public repository of xenografts enables discovery and randomized phase II-like trials in mice.

Cancer Cell 29, 574-586 (2016)
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More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acute Lymphoblastic-leukemia; Cancer Xenografts; Tumor Xenografts; Gene-expression; Clinical-trial; Models; Heterogeneity; Inhibition; Resistance; Mechanisms
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Journal Cancer Cell
Quellenangaben Volume: 29, Issue: 4, Pages: 574-586 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501590-001
DOI 10.1016/j.ccell.2016.03.008
WOS ID WOS:000373854600019
Scopus ID 84962740421
PubMed ID 27070704
Erfassungsdatum 2016-04-18
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