2019
DOI: 10.1101/790246
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Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis

Abstract: Patient-Derived Xenografts (PDXs) are tumor-in-mouse models for cancer. PDX collections, such as those supported by the NCI PDXNet program, are powerful resources for preclinical therapeutic testing. However, variations in experimental design and analysis procedures have limited interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three pre-validated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Center… Show more

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Cited by 4 publications
(6 citation statements)
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“…Thus, a given PDX generally represents the tumor of origin with high fidelity. 40 , 46 , 47 , 103 , 104 However, in patients, several biological factors can lead to heterogeneity in breast cancer tumors and affect a tumor’s response to therapy including tumor stage, location, grade/stage, and race/ethnicity (Mermut et al., 2021). Treatment of tumors also affects a tumor’s expression pattern 105 , 106 and its subsequent response to therapy.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Thus, a given PDX generally represents the tumor of origin with high fidelity. 40 , 46 , 47 , 103 , 104 However, in patients, several biological factors can lead to heterogeneity in breast cancer tumors and affect a tumor’s response to therapy including tumor stage, location, grade/stage, and race/ethnicity (Mermut et al., 2021). Treatment of tumors also affects a tumor’s expression pattern 105 , 106 and its subsequent response to therapy.…”
Section: Discussionmentioning
confidence: 99%
“… 39 We and others have shown remarkable biological consistency between patient tumors and their corresponding PDX with respect to histology, cellular heterogeneity, biomarker expression, mutations, genomic copy number alterations, variant allele frequencies, and mRNA expression patterns. 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 Most importantly, we and others have made progress in demonstrating that treatment responses in PDX are qualitatively similar to those of the tumor of origin. 40 , 42 , 43 Based on these commonalities, and the availability of a comparatively large collection of TNBC PDX, we hypothesized that a collection of PDX models can be used as a cohort comparable in size to many phase 1/2 human cohorts in clinical trials (n = 30+).…”
Section: Introductionmentioning
confidence: 86%
“…More recently, patient-derived xenograft (PDX) models of human breast cancer have emerged as potential surrogates for their tumor of origin. We and others have shown remarkable biological consistency between patient tumors and their corresponding PDX with respect to histology, cellular heterogeneity, biomarker expression, mutations, genomic copy number alterations, variant allele frequencies, and mRNA expression patterns (Dobrolecki et al, 2016;Echeverria et al, 2018;Evrard et al, 2019;Powell et al, 2020;Savage et al, 2020;Whittle et al, 2015;Woo et al, 2019;Zhang et al, 2013a). Most importantly, we and others have made progress in demonstrating that treatment responses in PDX are qualitatively similar to those of the tumor-of-origin (Savage et al, 2020;Whittle et al, 2015;Zhang et al, 2013a).…”
Section: Introductionmentioning
confidence: 76%
“…All raw FASTQ files were subjected to QC verification by FASTQC (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and were trimmed for adapter sequences with TrimGalore (https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/). Whole Exome FASTQ files were processed using the Tumor-Only Variant Calling pipeline (Evrard et al, 2019) developed by the Jackson Laboratory for PDXNet hosted on the Cancer Genomics Cloud. This pipeline uses Xenome (Conway et al, 2012) to separate human epithelial reads and mouse stromal reads, then aligns human reads against the GRCh38 human genome using bwa (Li, 2013).…”
Section: Dna Sequencing Data Processingmentioning
confidence: 99%
“…PDX models are well recognized in academic laboratories, pharmaceutical institutions, and specialized commercial organizations as having the ability to recapitulate genomics, transcriptomics, proteomics, and metabolomics of the parental tumor tissue [1,2]. Recently, these models have been successfully used in preclinical studies to identify potential biomarkers for drug response and resistance, and to measure tumor evolution in response to treatment [3,4]. Favorable outcomes demonstrated using PDX models could be used as ideal models for preclinical research and clinical translation studies.…”
Section: Main Textmentioning
confidence: 99%