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Organoid Cultures Derived from Patients with Advanced Prostate Cancer
Open accessAbstract
The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.
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“Tumor tissue, derived from either biopsies or surgical resections, is also typically processed akin to normal tissue to isolate tumour cells to grow as organoids16,49–51.”
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Metadata
- Authors
- Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., Dowling, C., Wanjala, J. N., Undvall, E. A., Arora, V. K., Wongvipat, J., Kossai, M., Ramazanoglu, S., Barboza, L. P., Di, W., Cao, Z., Zhang, Q. F., Sirota, I., Ran, L., MacDonald, T. Y., Beltran, H., Mosquera, J.-M., Touijer, K. A., Scardino, P. T., Laudone, V. P., Curtis, K. R., Rathkopf, D. E., Morris, M. J., Danila, D. C., Slovin, S. F., Solomon, S. B., Eastham, J. A., Chi, P., Carver, B., Rubin, M. A., Scher, H. I., Clevers, H., Sawyers, C. L., & Chen, Y.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- NewYork–Presbyterian Hospital (US)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Corresponding author
- Sawyers, Charles L.
- Chen, Yu
- ORCID
- Gao, Dong
- Vela, Ian
- Sboner, Andrea
- Karthaus, Wouter R.
- Gopalan, Anuradha
- Dowling, Catherine
- Arora, Vivek K.
- Di, Wei
- Cao, Zhen
- Sirota, Inna
- Ran, Leili
- Beltran, Himisha
- Scardino, Peter T.
- Laudone, Vincent P.
- Rathkopf, Dana E.
- Morris, Michael J.
- Danila, Daniel C.
- Slovin, Susan F.
- Solomon, Stephen B.
- Chi, Ping
- Carver, Brett
- Rubin, Mark A.
- Scher, Howard I.
- Clevers, Hans
- Sawyers, Charles L.
- Chen, Yu
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 159
- Issue
- 1
- Pages
- 176-187
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4237931
- OpenAlex
- W2059586354
- Cited by
- 1,559
- References
- 50
- Citations by year
- 2026: 110 · 2025: 117 · 2024: 138 · 2023: 145 · 2022: 155 · 2021: 172 · 2020: 180 · 2019: 131 · 2018: 131 · 2017: 120 · 2016: 87 · 2015: 67 · 2014: 5
- FWCI
- 73.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- U.S. Department of Defense (W81XWH, W81XWH1010197)
- American Association for Cancer Research (SU2C-AACR-DT0712)
- Prostate Cancer Foundation (SU2C-AACR-DT0712)
- Memorial Sloan-Kettering Cancer Center (P50CA092629)
- Movember Foundation
- National Institutes of Health (W81XWH, UL1TR000457)
- Stand Up To Cancer (SU2C-AACR-DT0712)
- National Cancer Institute (R01CA182503, K08CA151660, R01CA116337, CA155169-01A1, K08CA140946, R01CA155169, P30CA008748, P50CA092629, R01CA193837)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- prostate cancer, organoids, circulating tumor cells, 3D organoid culture, TMPRSS2-ERG fusion, SPOP mutations, FOXA1, PIK3R1, DNA repair mutations, p53 deficiency, mutational burden, advanced prostate cancer
- MeSH terms
- Humans, Male, Neoplasm Metastasis, Organoids, Pharmacology, Prostatic Neoplasms, Tumor Suppressor Proteins, Culture Techniques, Heterografts
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