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Patient derived organoids to model rare prostate cancer phenotypes.

TitlePatient derived organoids to model rare prostate cancer phenotypes.
Publication TypeJournal Article
Year of Publication2018
AuthorsPuca 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 LDayal, McNary TJ, Rosati R, Tagawa ST, Nanus DM, Mosquera JMiguel, Sawyers CL, Chen Y, Inghirami G, Rao RA, Grandori C, Elemento O, Sboner A, Demichelis F, Rubin MA, Beltran H
JournalNat Commun
Volume9
Issue1
Pagination2404
Date Published2018 Jun 19
ISSN2041-1723
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.

DOI10.1038/s41467-018-04495-z
Alternate JournalNat Commun
PubMed ID29921838
PubMed Central IDPMC6008438
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States
U54 CA210184 / CA / NCI NIH HHS / United States