Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer
Autor: | Suk Hyung Lee, Hikmat Al-Ahmadie, Alanna B. Williams, James M. McKiernan, Cory Abate-Shen, Wenhuo Hu, Mitchell C. Benson, Mark V. Silva, Barry S. Taylor, Kwanghee Kim, Eugene J. Pietzak, Sarah K. Bergren, La Mont J. Barlow, Christopher B. Anderson, Jonathan A. Coleman, Cyriac Kandoth, David B. Solit, Michael M. Shen, Justin T. Matulay, Chee Wai Chua, Tomasz Owczarek |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male DNA Copy Number Variations Cell Survival Transplantation Heterologous Context (language use) Antineoplastic Agents Disease Biology Somatic evolution in cancer General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice Mice Inbred NOD medicine Organoid Drug response Tumor Cells Cultured Animals Humans In patient Precision Medicine Aged Aged 80 and over Bladder cancer Cancer Middle Aged medicine.disease Organoids Disease Models Animal 030104 developmental biology Urinary Bladder Neoplasms Mutation Cancer research Female |
Zdroj: | Cell. 173(2) |
ISSN: | 1097-4172 |
Popis: | Summary Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo . Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine. |
Databáze: | OpenAIRE |
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