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

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. •PRoXe is an open-source repository of leukemia and lymphoma xenografts•PDXs capture transcriptional, genetic, and phenotypic disease diversity•Randomized phase II-like preclinical drug trials are feasible using PDXs•PDXs facilitate biomarker development and testing of relapsed/refractory disease Townsend et al. create a large, publicly available repository of leukemia and lymphoma patient-derived xenografts with well-characterized molecular and clinical information, and illustrate the utility of this repository by performing a preclinical in vivo study that mimics randomized human clinical trials.