Molecular subtype-specific breast cancer organoids: development of an FGF-free estradiol valerate culture system for precision drug screening

作者：Cheng Zhang, Bing Han, Zhihua Jia, M Y Liu, Yanxia Li, Jie Xu, Jie Zheng, Yajing Sun, Yuting Le, Shupeng Zhang, Zhijiang Shao, Jian Wang, X. L. Liu · 发表于：Cancer Cell International · 年份：2026 · DOI：10.1186/s12935-025-04160-8 · 研究领域：Cancer Cells and Metastasis、3D Printing in Biomedical Research、Cancer, Stress, Anesthesia, and Immune Response

Breast cancer, a prevalent malignancy among women, exhibits high heterogeneity, highlighting the critical need for personalized treatment strategies. Breast cancer organoids (BCOs), an emerging in vitro research tool, closely mimic the biological characteristics of tumors and demonstrate distinct differences in therapeutic response, prognosis, and biological features. However, the incomplete culture system of BCOs is still a challenging aspect of current research. In order to further optimize the existing culture formula of BCOs, molecular subtype characteristics in most cases. Through literature review and screening of key factors, we developed an FGF-free estradiol we collected tumor tissue samples from breast cancer patients with various molecular subtypes, including Luminal A, Luminal B, HER2 overexpressing (HER2+), and triple-negative breast cancer (TNBC). The samples were extracted and cultured using commercially available media. We observed that some media failed to sustain the growth of breast cancer organoids, while others, although supporting organoid survival, led to the loss of parental valerate (EV) culture system. Using triple-positive breast cancer samples, we optimized the concentration of EV. Our results indicated that 0, 10, and 20 µM EV maintained normal organoid growth, whereas 50 µM EV promoted adherent differentiation, which is detrimental to long-term organoid culture. Further analysis revealed that 20 µM EV not only preserved the organoid cellular morp...