Key Takeaways & Executive Findings
- •• Breast cancer organoids recapitulate tumor heterogeneity and microenvironment, offering a superior platform for drug sensitivity testing compared to traditional 2D cell lines. • Organoid-based drug screening has shown clinical promise in guiding personalized chemotherapy, targeted therapy, and immunotherapy for breast cancer patients. • Current limitations include low establishment efficiency, lack of vascularization, and incomplete mimicry of in vivo metabolic microenvironment, hindering clinical translation. • Future advances in culture techniques and co-culture systems are essential to enhance the reliability and applicability of breast cancer organoids in precision oncology.
Abstract
BACKGROUND: Breast cancer organoids, as a novel in vitro model, can not only simulate the biological characteristics of breast cancer but also to some extent reproduce the impact of the tumor microenvironment on the tumor, facilitating research on breast cancer and further promoting precision medicine. OBJECTIVE: To review the application status of breast cancer organoids in the field of therapeutic drugs, including chemotherapy, targeted therapy, and immunotherapy, over the past few years, and to discuss the existing limitations in order to further promote their application in breast cancer treatment. METHODS: The first author conducted a search in the China National Knowledge Infrastructure (CNKI) and PubMed databases in June 2025 for relevant literature published from January 2010 to June 2025. Chinese search terms included '类器官，乳腺类器官，乳腺癌类器官，乳腺癌模型实验验证，精准治疗，靶向治疗，化疗，免疫治疗，药物敏感性'; English search terms included 'organoid, breast organoid, breast cancer organoid, breast cancer experimental model, precision medicine, targeted therapy, chemotherapy, immunotherapy, drug sensitivity'. A total of 58 articles were included for review. RESULTS AND CONCLUSION: (1) Compared with traditional breast cancer cell experiments, which lack verification of tissue structure and cell-cell interactions as well as in vivo microenvironment, breast cancer organoids have diverse sources of primary tumor cells and continuously innovating culture systems. They can simulate cell-cell interactions and reproduce the biological characteristics of breast cancer and its tumor microenvironment, making breast cancer organoids one of the most promising tools in breast cancer research. This also provides greater potential for improving treatment resistance in clinical breast cancer patients through drug sensitivity screening. (2) The application of drug sensitivity test results from breast cancer organoids in clinical practice has yielded promising outcomes. By testing drug sensitivity in breast cancer organoids to common chemotherapeutic agents, targeted drugs, and immunotherapeutic drugs, the antitumor mechanisms and synergistic effects of multiple drugs can be verified, avoiding the use of drugs with primary resistance and high toxicity in patients, thereby enabling personalized treatment plans and evidence-based precision medicine strategies. (3) Breast cancer organoids still have limitations in practical applications such as drug screening and treatment, including low model construction success rates, difficulty in model growth, and lack of angiogenesis processes. To overcome these limitations, it is necessary to increase the source tissue volume, improve the culture system, and innovate culture techniques, which will facilitate comprehensive therapeutic drug selection through breast cancer organoids and aid in personalized precision medicine.
1. Introduction
Breast cancer has become the most common malignancy among women worldwide, with a high mortality rate. In recent years, advances in targeted therapy and immunotherapy have significantly improved progression-free survival and overall treatment outcomes for some patients. However, the risk of recurrence and metastasis still leads to poor prognosis in a subset of patients, and the 5-year survival rate for advanced breast cancer remains low. The instability of gene expression, tumor heterogeneity, and differences in the tumor microenvironment significantly affect treatment efficacy. Therefore, developing novel and practical tumor models to assess drug sensitivity is a potential strategy. Combining existing model validation with drug sensitivity test results to screen individualized therapeutic drugs is expected to further prolong the survival of cancer patients.
Traditional cell experiments have many limitations: they lack tissue structure and cell-cell interactions, cannot reproduce the in vivo microenvironment, and their results are easily influenced by specific cell lines and culture conditions. Breast organoids, as a novel in vitro model, can be classified into normal breast, breast cancer, and benign breast tumor types. Among them, breast cancer organoids can simulate the in vivo tumor microenvironment and maintain high genetic stability, and have been widely used for drug efficacy evaluation, supporting individualized and precise treatment of breast cancer.
Although existing reviews have discussed breast cancer organoids from different perspectives, most have a single viewpoint and lack comprehensive and in-depth summaries of drug validation. An increasing number of studies use breast cancer organoid models to assess drug sensitivity, providing preliminary evidence for clinical medication. These studies cover conventional targeted therapy, endocrine therapy drugs, and emerging immunotherapeutic agents. This review will focus on this theme, systematically summarizing the existing evidence of breast cancer organoids in drug validation, elaborating on their advantages and innovations, and discussing current limitations, aiming to contribute to the translation from bench to bedside.
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Mou Jiancheng, Luo Jie, Liu Haotian, Yang Zhuotao, Mu Yuxiao, Qian Da, Meng Xuli (2026). Application and prospects of precision-medicine-driven breast cancer organoids in therapeutic drug discovery. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21359
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Frequently Asked Questions
What are breast cancer organoids and why are they important?
Breast cancer organoids are three-dimensional in vitro models derived from patient tumor cells that self-organize into structures mimicking the original tumor's architecture and genetic profile. They are important because they retain tumor heterogeneity and microenvironment interactions, making them valuable for drug sensitivity testing and personalized treatment planning.
How are breast cancer organoids used in drug sensitivity testing?
Breast cancer organoids are exposed to various chemotherapeutic, targeted, and immunotherapeutic agents to assess their efficacy. The results help identify the most effective drugs for individual patients, avoiding ineffective treatments and reducing adverse effects, thereby guiding precision medicine.
What are the current limitations of breast cancer organoid models?
Current limitations include low success rates in establishing organoids, difficulty in long-term growth, lack of vascularization, and incomplete simulation of the in vivo metabolic microenvironment. These factors can affect the accuracy of drug response predictions and limit clinical translation.
What is the future outlook for breast cancer organoids in precision medicine?
With advancements in culture techniques, such as co-culture with stromal cells and microfluidic systems, breast cancer organoids are expected to better recapitulate the tumor microenvironment. This will enhance their predictive value and facilitate broader clinical application in personalized therapy.
How do breast cancer organoids compare to traditional 2D cell lines?
Unlike 2D cell lines, organoids preserve the three-dimensional architecture, cell-cell interactions, and genetic heterogeneity of the original tumor. This makes them more physiologically relevant and better predictors of drug response, although they are more complex and costly to maintain.
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