The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice
Cancer Cell , Volume 29 - Issue 4 p. 574- 586
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.
|Novartis Institutes for Biomedical Research, Cambridge, MA, USA, Novartis Institutes for Biomedical Research, Basel, Switzerland|
|This work was funded by the The Netherlands Organisation for Scientific Research (NWO); grant id nwo/639.072.309 - Statistical Models for Structural Genetic Variants in the Genome of the Netherlands|
|Organisation||Life Sciences and Health|
Townsend, E.C, Murakami, M.A, Christodoulou, A, Christie, A.L, Köster, J, DeSouza, T.A, … Weinstock, D.M. (2016). The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice. Cancer Cell, 29(4), 574–586. doi:10.1016/j.ccell.2016.03.008