Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor Intrinsic Characteristics.

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 TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBC). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibit signatures of aggressive MYC-driven, basal-like breast cancers and are largely comprised of luminal progenitor (LP)-like cells. The TNBC LP-like cells are distinct from normal LPs and exhibit 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.

SIGNIFICANCE:

A comprehensive analysis of patient-derived organoids of TNBC provides insights into cellular heterogeneity and mechanisms of tumorigenesis at the single-cell level.

• Authors: Sonam Bhatia, Melissa Kramer, Suzanne Russo, Payal Naik, Gayatri Arun, Kyle Brophy, Peter Andrews, Cheng Fan, Charles M Perou, Jonathan Preall, Taehoon Ha, Dennis Plenker, David A Tuveson, Arvind Rishi, John E Wilkinson, W Richard McCombie, Karen Kostroff, David L Spector
• Journal: Cancer research (Cancer Res) Vol. 82 Issue 7 Pg. 1174-1192 (04 01 2022) ISSN: 1538-7445 [Electronic] United States
• PMID: 35180770 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Proto-Oncogene Proteins c-myc

Topics

• Cell Line, Tumor
• Humans
• Organoids (pathology)
• Precision Medicine
• Proto-Oncogene Proteins c-myc (metabolism)
• Signal Transduction
• Triple Negative Breast Neoplasms (pathology)