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Patient derived organoids to model rare prostate cancer phenotypes
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018)
- Publication Year :
- 2017
-
Abstract
- A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.
- Subjects :
- 0301 basic medicine
Epigenomics
Male
Cell Survival
Concordance
Science
Knockout
General Physics and Astronomy
Antineoplastic Agents
Mice, SCID
SCID
General Biochemistry, Genetics and Molecular Biology
Cell Line
Transcriptome
03 medical and health sciences
Prostate cancer
Mice
Mice, Inbred NOD
Cell Line, Tumor
Organoid
Medicine
Animals
Humans
lcsh:Science
Mice, Knockout
Multidisciplinary
Tumor
business.industry
Mechanism (biology)
Gene Expression Profiling
EZH2
Prostate
Prostatic Neoplasms
General Chemistry
Genomics
medicine.disease
Phenotype
Xenograft Model Antitumor Assays
Organoids
Neuroendocrine Tumors
030104 developmental biology
Cancer research
Inbred NOD
lcsh:Q
business
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....79bd48d35951ecb52896f63fc14b069b