Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York.
University of North Carolina, Lineberger Comprehensive Cancer Center, Department of Genetics, Chapel Hill, North Carolina.
Cancer Res. 2022 Apr 1;82(7):1174-1192. doi: 10.1158/0008-5472.CAN-21-2807.
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.
A comprehensive analysis of patient-derived organoids of TNBC provides insights into cellular heterogeneity and mechanisms of tumorigenesis at the single-cell level.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌，患者预后较差，这突显了对靶向治疗和更好的模型系统的未满足的临床需求。在这里，我们开发并全面描述了一个多样化的正常和乳腺癌患者衍生类器官（PDO）生物库，重点是 TNBC。PDO 重现了患者肿瘤的内在特性，并且一部分 PDO 可以进行长期培养（LT-TNBC）。PDO 的单细胞分析确定了与癌症进展的不同方面相关的细胞类型和基因候选物。LT-TNBC 类器官表现出侵袭性 MYC 驱动的基底样乳腺癌的特征，并且主要由腔前体细胞（LP）样细胞组成。TNBC LP 样细胞与正常 LPs 不同，并且 NOTCH 和 MYC 信号的过度激活。总的来说，这项研究验证了 TNBC PDO 作为理解乳腺癌生物学和进展的强大模型，为个性化医学和量身定制的治疗选择铺平了道路。
对 TNBC 患者衍生类器官的全面分析提供了在单细胞水平上对细胞异质性和肿瘤发生机制的深入了解。
