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Updated: Mar 22, 2026
Generation of a Liver Orthotopic Human Uveal Melanoma Xenograft Platform in Immunodeficient Mice
Published on: November 6, 2019
The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice
Elizabeth C Townsend1, Mark A Murakami1, Alexandra Christodoulou1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 450 Brookline Avenue, Dana 510B, MA 02215, USA.
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.
Insights
Patient-derived xenografts (PDX) in mice can efficiently predict drug efficacy in human cancer trials. A new repository of leukemia and lymphoma PDXs aids in identifying effective cancer therapies and biomarkers.
Area of Science:
- Oncology
- Translational Research
- Biomedical Science
Background:
- High failure rate of preclinical cancer drugs in human trials due to insufficient efficacy.
- Need for predictive models to assess therapeutic activity across diverse tumor types.
Purpose of the Study:
- To establish a comprehensive, public repository of leukemia and lymphoma patient-derived xenografts (PDX).
- To demonstrate the utility of PDX models in adequately powered studies for evaluating drug efficacy and identifying biomarkers.
Main Methods:
- Creation of the Public Repository of Xenografts (PRoXe), a large, well-characterized collection of leukemia and lymphoma PDXs.
- Orthotopic engraftment of PDXs in mice.
- Conducting large-scale studies mimicking human randomized clinical trials using PDX models.
Main Results:
- Demonstrated that large studies of acute leukemia PDXs can effectively characterize drug efficacy.
- Identified transcriptional, functional, and proteomic biomarkers from PDX models.
- Successfully evaluated therapies in both treatment-naive and relapsed/refractory disease models.
Conclusions:
- Patient-derived xenografts in mice offer an efficient platform for predicting drug efficacy in human cancer.
- The PRoXe repository facilitates robust evaluation of therapeutic agents and biomarker discovery in hematologic malignancies.
- PDX models can accelerate the development of effective cancer treatments.
