@article{a24885b76dcd4ef2b3d03013c2e0f3bd,
title = "Patient derived organoids to model rare prostate cancer phenotypes",
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.",
author = "Loredana Puca and Rohan Bareja and Davide Prandi and Reid Shaw and Matteo Benelli and Karthaus, {Wouter R.} and Judy Hess and Michael Sigouros and Adam Donoghue and Myriam Kossai and Dong Gao and Joanna Cyrta and Verena Sailer and Aram Vosoughi and Chantal Pauli and Yelena Churakova and Cynthia Cheung and Deonarine, {Lesa Dayal} and McNary, {Terra J.} and Rachele Rosati and Tagawa, {Scott T.} and Nanus, {David M.} and Mosquera, {Juan Miguel} and Sawyers, {Charles L.} and Yu Chen and Giorgio Inghirami and Rao, {Rema A.} and Carla Grandori and Olivier Elemento and Andrea Sboner and Francesca Demichelis and Rubin, {Mark A.} and Himisha Beltran",
note = "Funding Information: We acknowledge assistance from the Molecular Cytology Core Facility at Memorial Sloan-Kettering Cancer Center (NIH Core Grant P30 CA 008748), the Translational Research Program at WCMC Pathology and Laboratory Medicine, and the WCM CLC Genomics and Epigenomics Core Facility. This study was supported by the Prostate Cancer Foundation (L.P., H.B.), American Italian Cancer Foundation (L.P.), European Research Council ERCCoG648670 (F.D.), Damon Runyon Cancer Research Foundation CI-67-13 (H.B.), Starr Cancer Consortium I7-A771 (Y.C., M.A.R, H.B.), Department of Defense PCRP PC121341 (H.B.), PC160264 (H.B), PC131961 (D.M.N., S.T.T., H.B.), and the National Cancer Institute 1U54CA210184-01 (H.B.) and WCM Prostate Cancer SPORE 1 P50 CA211024-01A1 (J.M.M., O.E., H.B.). Funding Information: The authors thank Drs. Ari Melnick and Wendy Beguelin at Weill Cornell Medicine for sharing short-harpin EZH2 plasmids. We acknowledge assistance from the Molecular Cytology Core Facility at Memorial Sloan-Kettering Cancer Center (NIH Core Grant P30 CA 008748), the Translational Research Program at WCMC Pathology and Laboratory Medicine, and the WCM CLC Genomics and Epigenomics Core Facility. This study was supported by the Prostate Cancer Foundation (L.P., H.B.), American Italian Cancer Foundation (L.P.), European Research Council ERCCoG648670 (F.D.), Damon Runyon Cancer Research Foundation CI-67-13 (H.B.), Starr Cancer Consortium I7-A771 (Y.C., M.A.R, H.B.), Department of Defense PCRP PC121341 (H.B.), PC160264 (H.B), PC131961 (D.M.N., S.T.T., H.B.), and the National Cancer Institute 1U54CA210184-01 (H.B.) and WCM Prostate Cancer SPORE 1 P50 CA211024-01A1 (J.M.M., O.E., H.B.). Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04495-z",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
