Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts. Academic Article uri icon

Overview

abstract

  • 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. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

authors

publication date

  • April 24, 2020

Research

keywords

  • Carcinoma, Transitional Cell
  • Gene Expression Regulation, Neoplastic
  • Urinary Bladder Neoplasms
  • Urothelium

Identity

PubMed Central ID

  • PMC7181640

Scopus Document Identifier

  • 85083832953

Digital Object Identifier (DOI)

  • 10.1038/nmeth.3252

PubMed ID

  • 32332851

Additional Document Info

volume

  • 11

issue

  • 1