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Cancer Cell. 2016 Apr 11;29(4):574-586. doi: 10.1016/j.ccell.2016.03.008.

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

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 450 Brookline Avenue, Dana 510B, MA 02215, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 450 Brookline Avenue, Dana 510B, MA 02215, USA; Center for Functional Cancer Epigenomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
3
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
4
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
5
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
6
Center for Functional Cancer Epigenomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
7
Leukemia Division, MD Anderson Cancer Center, Houston, TX 77030, USA.
8
Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
9
Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
10
Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
11
Office of Research and Technology Ventures, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
12
Department of Hematology, Brigham and Women's Hospital, Boston, MA 02115, USA.
13
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
14
EFS Bourgogne Franche Comté, INSERM UMR1098, 25020 Besançon, France.
15
Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
16
Department of Pathology, Boston Children's Hospital, Boston, MA 02215, USA.
17
Molecular Biology Core Facility, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
18
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
19
Department of Pathology, Weill Cornell Medical College, New York, NY 10065, USA.
20
Functional Genomics and Leukemia Research, Sheba Medical Center, Tel Hashomer and Tel Aviv University, Ramat Gan, 52621, Israel.
21
Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistraße 25, 81377 Munich, Germany; Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Lindwurmstraße 4, 80337 Munich, Germany.
22
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
23
Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.
24
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
25
Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
26
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
27
Université Paris Descartes, Faculté de Médecine Sorbonne Paris Cité, 75005 Paris, France.
28
Department of Pathology, British Columbia Cancer Research Center, Vancouver V5Z 1H8, Canada.
29
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: dweinstock@partners.org.

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.

PMID:
27070704
PMCID:
PMC5177991
DOI:
10.1016/j.ccell.2016.03.008
[Indexed for MEDLINE]
Free PMC Article

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