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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

Corresponding Author

Keywords Acute Lymphoblastic-leukemia; Cancer Xenografts; Tumor Xenografts; Gene-expression; Clinical-trial; Models; Heterogeneity; Inhibition; Resistance; Mechanisms

ISSN (print) / ISBN 1535-6108

e-ISSN 1878-3686

Journal Cancer Cell

Quellenangaben Volume: 29, Issue: 4, Pages: 574-586

Publisher Cell Press

Publishing Place Cambridge, Mass.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Gene Vector (AGV)