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:
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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