GSE134292
Patient-Derived Xenografts of Upper Tract Urothelial Cell Carcinoma: a tool for precision medicine
Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. A major hurdle to the advancement of UTUC research is the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell lines models that reflect the heterogeneity of the human disease. Models demonstrated high genomic concordance with the tumors from which they were derived with muscle-invasive tumors more likely to successfully engraft. Treatment of PDX with chemotherapy recapitulated responses observed in the patients. Analysis of a S310F HER2 mutant PDX suggested that an antibody drug conjugate targeting HER2 would have superior efficacy to HER2-selective kinase inhibitors. In sum, the biologic and phenotypic concordance between patient and PDXs suggests that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients. Overall design: 80 samples of RNA-Seq