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; Himisha Beltran

doi:10.1038/s41467-018-04495-z

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 RosatiScott 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, Himisha Beltran

Research output: Contribution to journal › Article › peer-review

230 Scopus citations

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.

Original language	English (US)
Article number	2404
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04495-z
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-018-04495-z

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Puca, L., Bareja, R., Prandi, D., Shaw, R., Benelli, M., Karthaus, W. R., Hess, J., Sigouros, M., Donoghue, A., Kossai, M., Gao, D., Cyrta, J., Sailer, V., Vosoughi, A., Pauli, C., Churakova, Y., Cheung, C., Deonarine, L. D., McNary, T. J., ... Beltran, H. (2018). Patient derived organoids to model rare prostate cancer phenotypes. Nature communications, 9(1), Article 2404. https://doi.org/10.1038/s41467-018-04495-z

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, Inghirami, G, Rao, RA, Grandori, C, Elemento, O, Sboner, A, Demichelis, F, Rubin, MA & Beltran, H 2018, 'Patient derived organoids to model rare prostate cancer phenotypes', Nature communications, vol. 9, no. 1, 2404. https://doi.org/10.1038/s41467-018-04495-z

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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.",

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AU - Bareja, Rohan

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AU - Shaw, Reid

AU - Benelli, Matteo

AU - Karthaus, Wouter R.

AU - Hess, Judy

AU - Sigouros, Michael

AU - Donoghue, Adam

AU - Kossai, Myriam

AU - Gao, Dong

AU - Cyrta, Joanna

AU - Sailer, Verena

AU - Vosoughi, Aram

AU - Pauli, Chantal

AU - Churakova, Yelena

AU - Cheung, Cynthia

AU - Deonarine, Lesa Dayal

AU - McNary, Terra J.

AU - Rosati, Rachele

AU - Tagawa, Scott T.

AU - Nanus, David M.

AU - Mosquera, Juan Miguel

AU - Sawyers, Charles L.

AU - Chen, Yu

AU - Inghirami, Giorgio

AU - Rao, Rema A.

AU - Grandori, Carla

AU - Elemento, Olivier

AU - Sboner, Andrea

AU - Demichelis, Francesca

AU - Rubin, Mark A.

AU - Beltran, Himisha

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Patient derived organoids to model rare prostate cancer phenotypes

Abstract

ASJC Scopus subject areas

UN SDGs

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