Patient derived organoids to model rare prostate cancer phenotypes

Loredana Puca, Rohan Bareja, Davide Prandi, Reid Shaw, Matteo Benelli, Wouter R. Karthaus, Judy Hess, Michael Sigouros, Adam Donoghue, Myriam Kossai, Dong Gao, Joanna Cyrta, Verena Sailer, Aram Vosoughi, Chantal Pauli, Yelena Churakova, Cynthia Cheung, Lesa Dayal Deonarine, Terra J. McNary, Rachele Rosati, Scott T. Tagawa, David M. Nanus, Juan Miguel Mosquera, Charles L. Sawyers, Yu Chen, Giorgio Inghirami, Rema A. Rao, Carla Grandori, Olivier Elemento, Andrea Sboner, Francesca Demichelis, Mark A. Rubin and Himisha Beltran ()
Additional contact information
Loredana Puca: Weill Cornell Medicine
Rohan Bareja: Weill Cornell Medicine-New York Presbyterian Hospital
Davide Prandi: University of Trento
Reid Shaw: Cure First and SEngine Precision Medicine
Matteo Benelli: University of Trento
Wouter R. Karthaus: Memorial Sloan Kettering Cancer Center
Judy Hess: Weill Cornell Medicine
Michael Sigouros: Weill Cornell Medicine
Adam Donoghue: Weill Cornell Medicine
Myriam Kossai: Weill Cornell Medicine
Dong Gao: Memorial Sloan Kettering Cancer Center
Joanna Cyrta: Weill Cornell Medicine-New York Presbyterian Hospital
Verena Sailer: Weill Cornell Medicine-New York Presbyterian Hospital
Aram Vosoughi: Weill Cornell Medicine-New York Presbyterian Hospital
Chantal Pauli: Weill Cornell Medicine-New York Presbyterian Hospital
Yelena Churakova: Weill Cornell Medicine-New York Presbyterian Hospital
Cynthia Cheung: Weill Cornell Medicine-New York Presbyterian Hospital
Lesa Dayal Deonarine: Weill Cornell Medicine
Terra J. McNary: Weill Cornell Medicine-New York Presbyterian Hospital
Rachele Rosati: Cure First and SEngine Precision Medicine
Scott T. Tagawa: Weill Cornell Medicine
David M. Nanus: Weill Cornell Medicine
Juan Miguel Mosquera: Weill Cornell Medicine
Charles L. Sawyers: Memorial Sloan Kettering Cancer Center
Yu Chen: Memorial Sloan Kettering Cancer Center
Giorgio Inghirami: Weill Cornell Medicine
Rema A. Rao: Weill Cornell Medicine-New York Presbyterian Hospital
Carla Grandori: Cure First and SEngine Precision Medicine
Olivier Elemento: Weill Cornell Medicine
Andrea Sboner: Weill Cornell Medicine-New York Presbyterian Hospital
Francesca Demichelis: Weill Cornell Medicine-New York Presbyterian Hospital
Mark A. Rubin: Weill Cornell Medicine-New York Presbyterian Hospital
Himisha Beltran: Weill Cornell Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04495-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04495-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04495-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().