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

URL: https://www.ncbi.nlm.nih.gov/pubmed/35180770
DOI: 10.1158/0008-5472.CAN-21-2807

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 > cancer types > breast cancer
Investigative techniques and equipment > cell culture > cancer organoids
diseases & disorders > cancer > drugs and therapies > precision medicine
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
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 18 February 2022
Date Deposited: 23 Feb 2022 15:09
Last Modified: 15 Jun 2022 15:24
PMCID: PMC9135475
URI: https://repository.cshl.edu/id/eprint/40521

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