The Public Repository of Xenografts (ProXe) enables discovery and randomized phase II-like trials in mice

Abstract

Over 90% of drugs with preclinical activity fail to ultimately benefit patients. We hypothesized that adequately sized and appropriately powered, randomized phase II-like trials of patient-derived xenografts (PDX) could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment and made them available through an open-source web portal (www.PRoXe.org) that includes all de-identified information relevant to the xenografted specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs designed to mimic human randomized phase II trials are feasible and can generate transcriptional, functional and proteomic biomarkers as well as large numbers of in vivo models with acquired resistance. Investigators from >50 institutions have already accessed PRoXe.org and models have been shared between >20 centers