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 > 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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