| Title | The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu S-C, 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, A Look T, 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 |
| Journal | Cancer Cell |
| Volume | 29 |
| Issue | 4 |
| Pagination | 574-586 |
| Date Published | 2016 04 11 |
| ISSN | 1878-3686 |
| Keywords | Animals, Antineoplastic Agents, Biomarkers, Tumor, Cell Lineage, Female, Gene Expression Profiling, Genes, p53, Heterografts, Humans, Internet, Isoquinolines, Leukemia, Leukemia, Experimental, Lymphoma, Male, Mice, Mice, Inbred NOD, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Piperazines, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Proteome, Proto-Oncogene Proteins c-mdm2, Random Allocation, Randomized Controlled Trials as Topic, Research Design, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays |
| 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. |
| DOI | 10.1016/j.ccell.2016.03.008 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 27070704 |
| PubMed Central ID | PMC5177991 |
| Grant List | P30 AR069625 / AR / NIAMS NIH HHS / United States R01 CA193651 / CA / NCI NIH HHS / United States P50 CA206963 / CA / NCI NIH HHS / United States R01 CA213138 / CA / NCI NIH HHS / United States T32 HL116324 / HL / NHLBI NIH HHS / United States P01 CA066996 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA157644 / CA / NCI NIH HHS / United States R01 CA203721 / CA / NCI NIH HHS / United States R01 AR063962 / AR / NIAMS NIH HHS / United States R01 CA172387 / CA / NCI NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D.