Patient-derived triple-negative breast cancer organoids provide robust model systems that recapitulate tumor-intrinsic characteristics

Bhatia, Sonam, Kramer, Melissa, Russo, Suzanne, Naik, Payal, Arun, Gayatri, Brophy, Kyle, Andrews, Peter, Fan, Cheng, Perou, Charles M, Preall, Jonathan, Ha, Taehoon, Plenker, Dennis, Tuveson, David A, Rishi, Arvind, Wilkinson, John E, McCombie, W Richard, Kostroff, Karen, Spector, David L (February 2022) Patient-derived triple-negative breast cancer organoids provide robust model systems that recapitulate tumor-intrinsic characteristics. Cancer Research. ISSN 0008-5472

Abstract

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, highlighting the unmet clinical need for targeted therapies and better model systems. Here, we developed and comprehensively characterized a diverse biobank of normal and breast cancer patient-derived organoids (PDO) with a focus on TNBC. PDOs recapitulated patient tumor-intrinsic properties, and a subset of PDOs were propagated for long-term culture (LT-TNBCs). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibited signatures of aggressive MYC-driven, basal-like breast cancers and largely comprised luminal progenitor (LP)-like cells. The TNBC LP-like cells were distinct from normal LPs and exhibited hyperactivation of NOTCH and MYC signaling. Overall, this study validates TNBC PDOs as robust models for understanding breast cancer biology and progression, paving the way for personalized medicine and tailored treatment options.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders Investigative techniques and equipment diseases & disorders > neoplasms diseases & disorders > cancer > cancer types > breast cancer Investigative techniques and equipment > cell culture > cancer organoids Investigative techniques and equipment > cell culture organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > cancer > drugs and therapies organs, tissues, organelles, cell types and functions diseases & disorders > cancer > drugs and therapies > precision medicine organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction organs, tissues, organelles, cell types and functions > tissues types and functions diseases & disorders > cancer > cancer types
CSHL Authors:	Bhatia, Sonam Kramer, Melissa R. Russo, Suzanne Arun, Gayatri Andrews, Peter Preall, Jonathan Ha, Taehoon Tuveson, David A. Spector, David L. Naik, Payal Plenker, Dennis McCombie, W. Richard
Communities:	CSHL labs > Kinney lab CSHL labs > McCombie lab CSHL labs > Preall lab CSHL labs > Spector lab CSHL labs > Tuveson lab CSHL labs > Wigler lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Histology Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service CSHL Cancer Center Shared Resources > Organoid Service CSHL Cancer Center Shared Resources > Single-Cell Biology Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	18 February 2022
Date Deposited:	23 Feb 2022 15:09
Last Modified:	09 Feb 2024 17:15
PMCID:	PMC9135475
URI:	https://repository.cshl.edu/id/eprint/40521

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