Advances in Mammary Organoid Technology and Their Applications in Breast Cancer Research
TANG Ruolan, CAI Shang*
Mammary organoids, three-dimensional culture-derived miniature models of breast tissue, have become essential tools for advancing breast biology and breast cancer research. In recent years, this technology has evolved from early simple mammosphere cultures to more complex organoid systems with branched structures, progressively achieving functional mimicry. Notably, the development of a novel “mini-gland culture system” employs a dynamic three-dimensional co-culture approach that enables individual mammary stem cells to undergo sequential processes including spheroid formation, polarity establishment, symmetry breaking, branching morphogenesis, and simulated estrous cycling. This system effectively recapitulates the tree-like branched ductal architecture of the mammary gland, dynamic hormonal responses, lineage tracing of stem cells, and spatiotemporal regulation of tumor initiation, offering a high-fidelity platform for mechanistic studies of breast cancer and the development of personalized therapies. This article systematically reviews the evolution of organoid culture systems, highlights their key applications in studying breast cancer initiation, the invasion-metastasis cascade, and drug screening, and explores the technical advantages and future potential of the emerging mini-gland culture system in tumor biology research. Although current systems still face limitations such as a simplified microenvironment and challenges in humanization, organoids are expected to play increasingly significant roles in breast cancer precision medicine through the integration of multi-omics approaches, organoid-on-a-chip technologies, and artificial intelligence in the future.
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