Title | Patient derived organoids to model rare prostate cancer phenotypes. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | 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 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 |
Journal | Nat Commun |
Volume | 9 |
Issue | 1 |
Pagination | 2404 |
Date Published | 2018 06 19 |
ISSN | 2041-1723 |
Keywords | Animals, Antineoplastic Agents, Cell Line, Tumor, Cell Survival, Epigenomics, Gene Expression Profiling, Genomics, Humans, Male, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Neuroendocrine Tumors, Organoids, Phenotype, Prostate, Prostatic Neoplasms, Xenograft Model Antitumor Assays |
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. |
DOI | 10.1038/s41467-018-04495-z |
Alternate Journal | Nat Commun |
PubMed ID | 29921838 |
PubMed Central ID | PMC6008438 |
Grant List | R01 CA193837 / CA / NCI NIH HHS / United States P50 CA092629 / CA / NCI NIH HHS / United States U54 CA210184 / CA / NCI NIH HHS / United States R01 CA155169 / CA / NCI NIH HHS / United States R01 CA208100 / CA / NCI NIH HHS / United States P50 CA211024 / CA / NCI NIH HHS / United States U54 CA224079 / CA / NCI NIH HHS / United States U01 CA224044 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States K08 CA140946 / CA / NCI NIH HHS / United States |