# Patient derived organoids to model rare prostate cancer phenotypes

Article · Puca L, Bareja R, Prandi D, Shaw R, Benelli M, Karthaus WR, Hess J, Sigouros M, Donoghue A, Kossai M, Gao D, Cyrta J, Sailer V, Vosoughi A, Pauli C, Churakova Y, Cheung C, Deonarine LD, McNary TJ, Rosati R, Tagawa ST, Nanus DM, Mosquera JM, Sawyers CL, Chen Y and 8 more

- Archive id: doi:10.1038/s41467-018-04495-z
- Published: 2018-06-19
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-018-04495-z
- PMID: 29921838
- PMCID: PMC6008438
- Citations: 311
- Source URL: https://doi.org/10.1038/s41467-018-04495-z
- PDF: https://europepmc.org/articles/PMC6008438/pdf
- Provenance: europepmc

## 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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Organoids & Organ-on-Chip](https://space-kitty.com/topics/organoids)

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