Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis.

Document Type

Article

Publication Date

6-1-2020

Keywords

JGM, JAXCC

JAX Source

Cancer Res 2020 Jun 1; 80(11):2286-2297

Volume

80

Issue

11

First Page

2286

Last Page

2297

ISSN

1538-7445

PMID

32152150

DOI

https://doi.org/10.1158/0008-5472.can-19-3101

Abstract

Patient-derived xenografts (PDX) are tumor-in-mouse models for cancer. PDX collections, such as the NCI PDXNet, are powerful resources for preclinical therapeutic testing. However, variations in experimental and analysis procedures have limited interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three prevalidated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Centers using independently selected standard operating procedures. Each PDTC was able to correctly identify the sensitive, resistant, and intermediate models, and statistical evaluations were concordant across all groups. We also developed and benchmarked optimized PDX informatics pipelines, and these yielded robust assessments across xenograft biological replicates. These studies show that PDX drug responses and sequence results are reproducible across diverse experimental protocols. In addition, we share the range of experimental procedures that maintained robustness, as well as standardized cloud-based workflows for PDX exome-sequencing and RNA-sequencing analyses and for evaluating growth. SIGNIFICANCE: The PDXNet Consortium shows that PDX drug responses and sequencing results are reproducible across diverse experimental protocols, establishing the potential for multisite preclinical studies to translate into clinical trials.

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