ArticleCancer medicine2025
Barcoded Orthotopic Patient-Derived Head & Neck Squamous Cell Carcinoma Model Demonstrating Clonal Stability and Maintenance of Cancer Driver Mutational Landscape.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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5 authors.
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Abstract
objectiveTo illustrate a new barcoded orthotopic patient-derived xenograft (PDX) mouse model where one can investigate phenotypic effects of single-cell level gene manipulation in a pooled format. To address some concerns of current PDX mouse models of head and neck squamous cell carcinoma (HNSCC): (1) genomic evolution with passage by generating high-purity cancer cells, which can also be utilized for other downstream applications, including cell culture-based studies, and (2) cost-effectiveness of current PDX models.
methodsTwo-millimeter tumor cubes from nine patients were implanted into immunodeficient mouse flanks subcutaneously. Purified tumor cells were obtained from subcutaneous xenografts. Various numbers of purified tumor cells were then injected into the lingual tissue of immunodeficient mice, and the lowest amount of cells needed to achieve a 100% orthotopic engraftment rate were identified. Clonal stability was tested using a lentiviral barcoding system. The orthotopic PDXs' genetic landscapes were characterized using whole exome sequencing.
resultsThis approach yielded an overall engraftment rate of 88.9%. The purification process increased cancer cell purity from 34% to 92%. Lingual injection of 100,000 purified tumor cells achieved a 100% orthotopic engraftment rate from purified subcutaneous PDX tumor cells while maintaining clonal and genetic stability.
conclusionOur study presents a barcoded orthotopic patient-derived xenograft model for head and neck squamous cell carcinoma with clonal stability. This model provides a way to study phenotypic effects of single cell level gene manipulation in a pooled format. The method can be adapted for in vitro work as well.
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