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Cell. 2018 Apr 5;173(2):515-528.e17. doi: 10.1016/j.cell.2018.03.017.

Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer.

Author information

1
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
2
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
3
Department of Urology, Columbia University Medical Center, New York, NY 10032, USA; New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA.
4
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
8
Department of Urology, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA; New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA.
9
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
10
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
11
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
12
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
13
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: mshen@columbia.edu.

Abstract

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.

KEYWORDS:

bladder cancer; clonal evolution; drug response; patient-derived organoids; patient-derived xenografts

PMID:
29625057
PMCID:
PMC5890941
DOI:
10.1016/j.cell.2018.03.017
[Indexed for MEDLINE]
Free PMC Article

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