Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts.

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ID: 104731
2020
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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.
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kim2020modelingnature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kim, Kwanghee;Hu, Wenhuo;Audenet, François;Almassi, Nima;Hanrahan, Aphrothiti J;Murray, Katie;Bagrodia, Aditya;Wong, Nathan;Clinton, Timothy N;Dason, Shawn;Mohan, Vishnu;Jebiwott, Sylvia;Nagar, Karan;Gao, Jianjiong;Penson, Alex;Hughes, Chris;Gordon, Benjamin;Chen, Ziyu;Dong, Yiyu;Watson, Philip A;Alvim, Ricardo;Elzein, Arijh;Gao, Sizhi P;Cocco, Emiliano;Santin, Alessandro D;Ostrovnaya, Irina;Hsieh, James J;Sagi, Irit;Pietzak, Eugene J;Hakimi, A Ari;Rosenberg, Jonathan E;Iyer, Gopa;Vargas, Herbert A;Scaltriti, Maurizio;Al-Ahmadie, Hikmat;Solit, David B;Coleman, Jonathan A;
Journal Nature communications
Year 2020
DOI
10.1038/s41467-020-15885-7
URL
Keywords
incidence recurrence antitubercular agents/therapeutic use* south africa/epidemiology tuberculosispulmonary/epidemiology

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