Tumor evolution and drug response in patient-derived organoid models of bladder cancer Journal Article


Authors: Lee, S. H.; Hu, W.; Matulay, J. T.; Silva, M. V.; Owczarek, T. B.; Kim, K.; Chua, C. W.; Barlow, L. J.; Kandoth, C.; Williams, A. B.; Bergren, S. K.; Pietzak, E. J.; Anderson, C. B.; Benson, M. C.; Coleman, J. A.; Taylor, B. S.; Abate-Shen, C.; McKiernan, J. M.; Al-Ahmadie, H.; Solit, D. B.; Shen, M. M.
Article Title: Tumor evolution and drug response in patient-derived organoid models of bladder cancer
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. A biobank of patient-derived bladder tumor organoids faithfully recapitulates features of human cancer and enables analysis of clonal evolution and drug responses. © 2018 Elsevier Inc.
Keywords: immunohistochemistry; adult; controlled study; human tissue; treatment response; aged; gene mutation; clinical feature; histopathology; mortality; squamous cell carcinoma; cisplatin; doxorubicin; erlotinib; fluorouracil; united states; gemcitabine; paclitaxel; methotrexate; cancer grading; cell proliferation; unindexed drug; hepatocyte nuclear factor 3alpha; transcription factor gata 3; gene expression profiling; morbidity; prevalence; immunofluorescence; tumor xenograft; bladder cancer; risk factor; histology; ifosfamide; vinblastine; carcinogenesis; docetaxel; drug response; cystectomy; cytokeratin; transurethral resection; mitomycin; transitional cell carcinoma; rapamycin; caucasian; neratinib; copy number variation; muscle invasive bladder cancer; azd 8055; selumetinib; clonal evolution; veliparib; cabazitaxel; cancer prognosis; trametinib; non muscle invasive bladder cancer; 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea; 8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1,2,4 triazolo[3,4 f][1,6]naphthyridin 3(2h) one; pictilisib; dovitinib; very elderly; human; male; female; priority journal; article; whole exome sequencing; erdafitinib; 4 (4 chlorophenyl) 2,3,9 trimethyl 6h thieno[3,2 f][1,2,4]triazolo[4,3 a][1,4]diazepine 6 acetic acid tert butyl ester; patient-derived xenografts; biobank; patient-derived organoids; gedatolisib; sapitinib
Journal Title: Cell
Volume: 173
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2018-04-05
Start Page: 515
End Page: 528.e17
Language: English
DOI: 10.1016/j.cell.2018.03.017
PROVIDER: scopus
PMCID: PMC5890941
PUBMED: 29625057
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    192 Coleman
  2. David Solit
    440 Solit
  3. Wenhuo Hu
    29 Hu
  4. Barry Stephen Taylor
    144 Taylor
  5. Cyriac Kandoth
    18 Kandoth
  6. Kwanghee   Kim
    13 Kim
  7. Eugene J Pietzak
    21 Pietzak