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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2016
Journal
Cancer Cell
Volume
29
Issue
4
Pages
574-86
Date Published
2016 04 11
ISSN
1878-3686
URL
DOI
10.1016/j.ccell.2016.03.008
PubMed ID
27070704
PubMed Central ID
PMC5177991
Links
Grant list
R01 CA193651 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
T32 HL116324 / HL / NHLBI NIH HHS / United States
P01 CA066996 / CA / NCI NIH HHS / United States
K08 CA181340 / CA / NCI NIH HHS / United States
R01 CA203721 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 CA172387 / CA / NCI NIH HHS / United States