ArticlePLoS computational biology2019
Whole genomes define concordance of matched primary, xenograft, and organoid models of pancreas cancer.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Application and prospect of organoid technology in breast cancer.Frontiers in immunology · 2024Pooled it
- A Patient-Derived Organ-on-Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Living Biobanks of Organoids: Valuable Resource for Translational Research.Biopreservation and biobanking · 2024Review
- The αvβ6 integrin specific virotherapy, Ad5British journal of cancer · 2024Article
- Defining and tracing subtypes of patient-derived xenograft models in pancreatic ductal adenocarcinoma.Cancer communications (London, England) · 2024Article
- Graphene Oxide Nanoparticles and Organoids: A Prospective Advanced Model for Pancreatic Cancer Research.International journal of molecular sciences · 2024Review
- Article
- Mutation divergence over space in tumour expansion.Journal of the Royal Society, Interface · 2023Article
- Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System.Cancers · 2023Review
- Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.Journal of experimental & clinical cancer research : CR · 2023Article
- Spatial Alignment of Organoids Tracking Subclonal Chemotherapy Resistance in Pancreatic and Ampullary Cancer.Bioengineering (Basel, Switzerland) · 2023Article
- Article
- Genomic heterogeneity in pancreatic cancer organoids and its stability with culture.NPJ genomic medicine · 2022Article
- Patient-derived parathyroid organoids as a tracer and drug-screening application model.Stem cell reports · 2022Article
- Review on Advanced Cancer Modeling for a Cancer Study.Current issues in molecular biology · 2022Article
- The pivotal application of patient-derived organoid biobanks for personalized treatment of gastrointestinal cancers.Biomarker research · 2022Review
- Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies.Gut and liver · 2022Article
- DNA-based copy number analysis confirms genomic evolution of PDX models.NPJ precision oncology · 2022Article
- Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among solid malignancies and improved therapeutic strategies are needed to improve outcomes. Patient-derived xenografts (PDX) and patient-derived organoids (PDO) serve as promising tools to identify new drugs with therapeutic potential in PDAC. For these preclinical disease models to be effective, they should both recapitulate the molecular heterogeneity of PDAC and validate patient-specific therapeutic sensitivities. To date however, deep characterization of the molecular heterogeneity of PDAC PDX and PDO models and comparison with matched human tumour remains largely unaddressed at the whole genome level. We conducted a comprehensive assessment of the genetic landscape of 16 whole-genome pairs of tumours and matched PDX, from primary PDAC and liver metastasis, including a unique cohort of 5 'trios' of matched primary tumour, PDX, and PDO. We developed a pipeline to score concordance between PDAC models and their paired human tumours for genomic events, including mutations, structural variations, and copy number variations. Tumour-model comparisons of mutations displayed single-gene concordance across major PDAC driver genes, but relatively poor agreement across the greater mutational load. Genome-wide and chromosome-centric analysis of structural variation (SV) events highlights previously unrecognized concordance across chromosomes that demonstrate clustered SV events. We found that polyploidy presented a major challenge when assessing copy number changes; however, ploidy-corrected copy number states suggest good agreement between donor-model pairs. Collectively, our investigations highlight that while PDXs and PDOs may serve as tractable and transplantable systems for probing the molecular properties of PDAC, these models may best serve selective analyses across different levels of genomic complexity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.