ArticleNeuro-oncology2020
Patient-derived xenografts of central nervous system metastasis reveal expansion of aggressive minor clones.
Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Single cell and spatial sequencing analysis of cancer associated fibroblasts in the brain metastasis tumor microenvironment.Communications biology · 2026Article
- ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
- Recurrent glioblastoma metastatic to the lumbar vertebra: A case report and literature review: Surgical oncology.Frontiers in oncology · 2023Article
- Establishment and genetically characterization of patient-derived xenograft models of cervical cancer.BMC medical genomics · 2022Article
- Patient-derived models of brain metastases recapitulate human disseminated disease.Cell reports. Medicine · 2022Article
- DNA-based copy number analysis confirms genomic evolution of PDX models.NPJ precision oncology · 2022Article
- Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance.Nature biomedical engineering · 2021Article
- Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology.Acta neuropathologica · 2020Article
- Novel Breast Cancer Brain Metastasis Patient-Derived Orthotopic Xenograft Model for Preclinical Studies.Cancers · 2020Article
- Circulating Tumor Cells Exhibit Metastatic Tropism and Reveal Brain Metastasis Drivers.Cancer discovery · 2020Article
- Building Equitable Cancer Research Infrastructure: Successful Transfer of Patient-Derived Xenograft Technology to a Historically Black University.Cancer control : journal of the Moffitt Cancer CenterArticle
- Brain metastasis patient-derived xenograft models to characterize the contribution of brain microenvironment to metastatic outgrowth.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
21 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dearth of relevant tumor models reflecting the heterogeneity of human central nervous system metastasis (CM) has hindered development of novel therapies.
methodsWe established 39 CM patient-derived xenograft (PDX) models representing the histological spectrum, and performed phenotypic and multi-omic characterization of PDXs and their original patient tumors. PDX clonal evolution was also reconstructed using allele-specific copy number and somatic variants.
resultsPDXs retained their metastatic potential, with flank-implanted PDXs forming spontaneous metastases in multiple organs, including brain, and CM subsequent to intracardiac injection. PDXs also retained the histological and molecular profiles of the original patient tumors, including retention of genomic aberrations and signaling pathways. Novel modes of clonal evolution involving rapid expansion by a minor clone were identified in 2 PDXs, including CM13, which was highly aggressive in vivo forming multiple spontaneous metastases, including to brain. These PDXs had little molecular resemblance to the patient donor tumor, including reversion to a copy number neutral genome, no shared nonsynonymous mutations, and no correlation by gene expression.
conclusionsWe generated a diverse and novel repertoire of PDXs that provides a new set of tools to enhance our knowledge of CM biology and improve preclinical testing. Furthermore, our study suggests that minor clone succession may confer tumor aggressiveness and potentiate brain metastasis.
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