The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice.
Fiche publication
Date publication
avril 2016
Journal
Cancer cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GARNACHE-OTTOU Francine
Tous les auteurs :
Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM
Lien Pubmed
Résumé
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.
Mots clés
Animals, Antineoplastic Agents, pharmacology, Biomarkers, Tumor, Cell Lineage, Female, Gene Expression Profiling, Genes, p53, Heterografts, Humans, Internet, Isoquinolines, pharmacology, Leukemia, metabolism, Leukemia, Experimental, drug therapy, Lymphoma, metabolism, Male, Mice, Mice, Inbred NOD, Molecular Targeted Therapy, Neoplasm Proteins, antagonists & inhibitors, Neoplasm Transplantation, Phenotype, Piperazines, pharmacology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, drug therapy, Proteome, Proto-Oncogene Proteins c-mdm2, antagonists & inhibitors, Random Allocation, Randomized Controlled Trials as Topic, methods, Research Design, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays
Référence
Cancer Cell. 2016 04;29(4):574-86