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Nat Commun. 2018 Jun 19;9(1):2404. doi: 10.1038/s41467-018-04495-z.

Patient derived organoids to model rare prostate cancer phenotypes.

Author information

1
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10021, USA.
2
Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10021, USA.
3
Englander Institute for Precision Medicine,, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY, 10021, USA.
4
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.
5
Center for Integrative Biology, University of Trento, 38123, Trento, Italy.
6
Cure First and SEngine Precision Medicine, Seattle, WA, 98109, USA.
7
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
8
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
9
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10021, USA. hip9004@med.cornell.edu.
10
Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10021, USA. hip9004@med.cornell.edu.
11
Englander Institute for Precision Medicine,, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY, 10021, USA. hip9004@med.cornell.edu.

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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