Breast cancer organoids: a precision platform for modeling heterogeneity and advancing personalized therapy

Abstract

Breast cancer remains the most prevalent malignancy among women worldwide, characterized by profound heterogeneity and therapeutic resistance that pose significant challenges to both research and clinical management. Breast cancer organoids (BCOs), as three-dimensional in vitro models derived from patient tissues, closely recapitulate the key structural, molecular, and heterogeneous characteristics of primary tumors, surpassing conventional models in fidelity and clinical relevance. This review systematically synthesizes the key advancements in BCO technology, encompassing standardized sample processing, optimized culture systems, and the integration of dynamic microfluidic platforms that better mimic the tumor microenvironment. Due to the high degree of genomic and phenotypic concordance between BCOs and their parental tumors, BCOs have proven indispensable in subtype-specific research, such as illuminating mechanisms of endocrine resistance in luminal tumors, uncovering metastatic pathways in HER2+ cancers, and identifying novel therapeutic vulnerabilities in triple-negative breast cancer. Furthermore, organoid-based metabolic and signaling pathway analyses have revealed new regulators of tumor progression. In the realm of clinical translation, BCOs are increasingly used for high-throughput drug screening and personalized drug sensitivity testing, guiding therapeutic decisions. The establishment of organoid biobanks and the implementation of standardized protocols are facilitating large-scale studies and multicenter collaborations. Despite ongoing challenges in microenvironment simulation and protocol standardization, the convergence of BCOs with emerging technologies, such as single-cell multi-omics, CRISPR screening, and engineered microenvironments, holds immense potential. With their unparalleled capacity to model tumor evolution and therapeutic responses, BCOs represent a paradigm shift in precision oncology, ultimately bridging the gap between basic research and individualized patient care.

Keywords

Breast cancer / Organoid / Tumor microenvironment / Personalized medicine / Drug screening / Precision oncology

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