The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice
Open accessAbstract
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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PDX models were engrafted in NSG mice and handled according to an IACUC-approved protocol.
“PDX models (supplemental Table 5, available on the Blood Web site) were engrafted in Nod.Cg-Prkdc scid IL2rg tm1Wjl /SzJ (NSG) mice purchased from The Jackson Laboratory and handled according to a Dana-Farber Cancer Institute's Institutional Animal Care and Use Committee-approved protocol (#13-034), as described previously.28”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [28]
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- Authors
- Townsend, E. C., Murakami, M. A., Christodoulou, A., Christie, A. L., Köster, 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., Intlekofer, 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., LeBoeuf, N. R., 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., Bertagnolli, M. M., Ritz, J., Brown, M., Long, H., Aster, J. C., Shipp, M. A., Griffin, J. D., & Weinstock, D. M.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Novartis (Switzerland) (CH)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Massachusetts General Hospital (US)
- Boston Children's Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- Weill Cornell Medicine (US)
- Tel Aviv University (IL)
- Helmholtz Munich (DE)
- University of Massachusetts Chan Medical School (US)
- Columbia University Irving Medical Center (US)
- BC Cancer Agency (CA)
- University of California, San Francisco (US)
- Broad Institute (US)
- Corresponding author
- Weinstock, David M.
- ORCID
- Townsend, Elizabeth C.
- Murakami, Mark A.
- Köster, Johannes
- DeSouza, Tiffany A.
- Morgan, Elizabeth A.
- Kallgren, Scott P.
- Liu, Huiyun
- Montero, Joan
- Stevenson, Kristen E.
- Andreeff, Michael
- Armand, Philippe
- Ballen, Karen K.
- Barzaghi-Rinaudo, Patrizia
- Cahill, Sarah
- Clark, Rachael A.
- Davids, Matthew S.
- DeAngelo, Daniel J.
- Dorfman, David M.
- Ebert, Benjamin L.
- Fisher, David C.
- Freedman, Arnold S.
- Galinsky, Ilene A.
- Garcia, Jacqueline S.
- Graubert, Timothy A.
- Halilovic, Ensar
- Harris, Marian H.
- Herbert, Zachary T.
- Horwitz, Steven M.
- Inghirami, Giorgio
- Intlekofer, Andrew M.
- Izraeli, Shai
- Jacobsen, Eric D.
- Jacobson, Caron A.
- Jeay, Sébastien
- Jeremias, Irmela
- Kelliher, Michelle A.
- Koch, Raphael
- Konopleva, Marina
- Kornblau, Steven M.
- Kung, Andrew L.
- Kupper, Thomas S.
- LeBoeuf, Nicole R.
- LaCasce, Ann S.
- Lees, Emma
- Li, Loretta S.
- Look, A. Thomas
- Murakami, Masato
- Neuberg, Donna
- Ng, Samuel Y.
- Odejide, Oreofe O.
- Orkin, Stuart H.
- Place, Andrew E.
- Ryan, Jeremy A.
- Sallan, Stephen E.
- Shoji, Brent
- Silverman, Lewis B.
- Soiffer, Robert J.
- Steensma, David P.
- Stegmaier, Kimberly
- Stone, Richard M.
- Thorner, Aaron R.
- Wadleigh, Martha
- Weng, Andrew P.
- Williams, David A.
- Wollison, Bruce M.
- Lane, Andrew A.
- Letai, Anthony
- Bertagnolli, Monica M.
- Ritz, Jerome
- Brown, Myles
- Long, Henry
- Aster, Jon C.
- Shipp, Margaret A.
- Griffin, James D.
- Weinstock, David M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 29
- Issue
- 4
- Pages
- 574-586
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC5177991
- OpenAlex
- W2334045973
- Cited by
- 295
- References
- 38
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 15 · 2023: 28 · 2022: 37 · 2021: 39 · 2020: 37 · 2019: 36 · 2018: 31 · 2017: 40 · 2016: 8
- FWCI
- 38.01
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-07-11)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Centrum Wiskunde & Informatica (CWI), the national research institute for mathematics and computer science in the Netherlands (submittedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- Gabrielle's Angel Foundation for Cancer Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- patient-derived xenografts, acute leukemia, lymphoma, drug efficacy, relapsed/refractory disease, biomarkers, mouse model, translational oncology
- MeSH terms
- Animals, Antineoplastic Agents, Female, Humans, Isoquinolines, Leukemia, Leukemia, Experimental, Lymphoma, Male, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Piperazines, Random Allocation, Research Design, Tissue Banks, Biomarkers, Tumor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Randomized Controlled Trials as Topic, Genes, p53, Mice, Inbred NOD, Cell Lineage, Internet, Proteome, Gene Expression Profiling, Xenograft Model Antitumor Assays, Mice, Proto-Oncogene Proteins c-mdm2, Molecular Targeted Therapy, Transcriptome, Heterografts
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