The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice.

Authors:
Elizabeth C Townsend Mark A Murakami Alexandra Christodoulou Amanda L Christie Johannes Köster Tiffany A DeSouza Elizabeth A Morgan Scott P Kallgren Huiyun Liu Shuo-Chieh Wu Olivia Plana Joan Montero Kristen E Stevenson Prakash Rao Raga Vadhi Michael Andreeff Philippe Armand Karen K Ballen Patrizia Barzaghi-Rinaudo Sarah Cahill Rachael A Clark Vesselina G Cooke Matthew S Davids Daniel J DeAngelo David M Dorfman Hilary Eaton Benjamin L Ebert Julia Etchin Brant Firestone David C Fisher Arnold S Freedman Ilene A Galinsky Hui Gao Jacqueline S Garcia Francine Garnache-Ottou Timothy A Graubert Alejandro Gutierrez Ensar Halilovic Marian H Harris Zachary T Herbert Steven M Horwitz Giorgio Inghirami Andrew M Intlekofer Moriko Ito Shai Izraeli Eric D Jacobsen Caron A Jacobson Sébastien Jeay Irmela Jeremias Michelle A Kelliher Raphael Koch Marina Konopleva Nadja Kopp Steven M Kornblau Andrew L Kung Thomas S Kupper Nicole R LeBoeuf Ann S LaCasce Emma Lees Loretta S Li A Thomas Look Masato Murakami Markus Muschen Donna Neuberg Samuel Y Ng Oreofe O Odejide Stuart H Orkin Rachel R Paquette Andrew E Place Justine E Roderick Jeremy A Ryan Stephen E Sallan Brent Shoji Lewis B Silverman Robert J Soiffer David P Steensma Kimberly Stegmaier Richard M Stone Jerome Tamburini Aaron R Thorner Paul van Hummelen Martha Wadleigh Marion Wiesmann Andrew P Weng Jens U Wuerthner David A Williams Bruce M Wollison Andrew A Lane Anthony Letai Monica M Bertagnolli Jerome Ritz Myles Brown Henry Long Jon C Aster Margaret A Shipp James D Griffin David M Weinstock

Cancer Cell 2016 04;29(4):574-586

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 450 Brookline Avenue, Dana 510B, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

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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http://dx.doi.org/10.1016/j.ccell.2016.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177991PMC
April 2016
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