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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Evrard YA,Srivastava A,Randjelovic J,Doroshow JH,Dean DA 2nd,Morris JS,Chuang JH,NCI PDXNet Consortium.doi
10.1158/0008-5472.CAN-19-3101subject
Has Abstractpub_date
2020-06-01 00:00:00pages
2286-2297issue
11eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-19-3101journal_volume
80pub_type
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