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

ABSTRACT: 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.

SUBMITTER: Townsend EC 

PROVIDER: S-EPMC5177991 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Townsend Elizabeth C EC   Murakami Mark A MA   Christodoulou Alexandra A   Christie Amanda L AL   Köster Johannes J   DeSouza Tiffany A TA   Morgan Elizabeth A EA   Kallgren Scott P SP   Liu Huiyun H   Wu Shuo-Chieh SC   Plana Olivia O   Montero Joan J   Stevenson Kristen E KE   Rao Prakash P   Vadhi Raga R   Andreeff Michael M   Armand Philippe P   Ballen Karen K KK   Barzaghi-Rinaudo Patrizia P   Cahill Sarah S   Clark Rachael A RA   Cooke Vesselina G VG   Davids Matthew S MS   DeAngelo Daniel J DJ   Dorfman David M DM   Eaton Hilary H   Ebert Benjamin L BL   Etchin Julia J   Firestone Brant B   Fisher David C DC   Freedman Arnold S AS   Galinsky Ilene A IA   Gao Hui H   Garcia Jacqueline S JS   Garnache-Ottou Francine F   Graubert Timothy A TA   Gutierrez Alejandro A   Halilovic Ensar E   Harris Marian H MH   Herbert Zachary T ZT   Horwitz Steven M SM   Inghirami Giorgio G   Intlekofer Andrew M AM   Ito Moriko M   Izraeli Shai S   Jacobsen Eric D ED   Jacobson Caron A CA   Jeay Sébastien S   Jeremias Irmela I   Kelliher Michelle A MA   Koch Raphael R   Konopleva Marina M   Kopp Nadja N   Kornblau Steven M SM   Kung Andrew L AL   Kupper Thomas S TS   LeBoeuf Nicole R NR   LaCasce Ann S AS   Lees Emma E   Li Loretta S LS   Look A Thomas AT   Murakami Masato M   Muschen Markus M   Neuberg Donna D   Ng Samuel Y SY   Odejide Oreofe O OO   Orkin Stuart H SH   Paquette Rachel R RR   Place Andrew E AE   Roderick Justine E JE   Ryan Jeremy A JA   Sallan Stephen E SE   Shoji Brent B   Silverman Lewis B LB   Soiffer Robert J RJ   Steensma David P DP   Stegmaier Kimberly K   Stone Richard M RM   Tamburini Jerome J   Thorner Aaron R AR   van Hummelen Paul P   Wadleigh Martha M   Wiesmann Marion M   Weng Andrew P AP   Wuerthner Jens U JU   Williams David A DA   Wollison Bruce M BM   Lane Andrew A AA   Letai Anthony A   Bertagnolli Monica M MM   Ritz Jerome J   Brown Myles M   Long Henry H   Aster Jon C JC   Shipp Margaret A MA   Griffin James D JD   Weinstock David M DM  

Cancer cell 20160401 4

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  ...[more]

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