The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice
Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
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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Citation: Cancer Cell. 2016 Apr 11;29(4):574-86. doi: 10.1016/j.ccell.2016.03.008. Link to article on publisher's site
Townsend, Elizabeth C.; Kelliher, Michelle A.; Roderick, Justine E.; and Weinstock, David M., "The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice" (2016). UMass Metabolic Network Publications. 48.