三阴性乳腺癌类器官模型的构建及其应用

Construction and Application of the Organoid Model for Triple-Negative Breast Cancer

摘要: 三阴性乳腺癌(Triple-Negative Breast Cancer, TNBC)是一种高侵袭性且预后较差的乳腺癌亚型，目前没有治疗有效的靶点，而针对其他类型乳腺癌的靶向药物往往对这种乳腺癌无效。类器官(Organoids)作为一种新型的体外细胞培养模型，因结构和功能与人体器官高度相似，在疾病建模、药物研发、精准医疗等方面拥有广泛的应用前景。本文系统综述了TNBC类器官模型的建立方式、构建方法、应用实例、应用方向及未来展望等内容进行阐述，在介绍TNBC类器官建立过程中所用到的组织来源、样本制备、培养基种类、培养条件等注意事项的基础上，着重分析了各种生物材料的应用；从类器官模型能够再现肿瘤特性、能够用于药物筛选及预测治疗反应、具有模拟体内微环境的功能等方面详述其应用；介绍了肿瘤微环境对类器官模型产生的影响，针对临床转化中存在的问题，分析了类器官模型应用于临床治疗时应当注意的一些问题。同时本文论述了TNBC类器官的构建策略与应用前景，并对其在个体化治疗中的潜力进行了展望。

Abstract: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with unfavorable prognosis. Currently, there are no effective therapeutic targets for TNBC, and targeted drugs effective against other breast cancer subtypes often fail to exert efficacy in TNBC treatment. Organoids, as a novel in vitro cell culture model, possess high structural and functional similarity to human organs, thereby holding broad application prospects in disease modeling, drug development, precision medicine, and other fields. This review systematically elaborates on the establishment methods, construction protocols, application cases, research directions, and future prospects of TNBC organoid models. On the basis of introducing key considerations in the establishment of TNBC organoids—including tissue sources, sample preparation, types of culture media, and culture conditions—it focuses on analyzing the application of various biomaterials. Furthermore, it details the applications of organoid models from three aspects: their capacity to recapitulate tumor characteristics, their utility in drug screening and prediction of therapeutic responses, and their function in simulating the in vivo microenvironment. This review also discusses the impact of the tumor microenvironment on organoid models, analyzes critical issues requiring attention when applying these models to clinical treatment in light of challenges in clinical translation, and expounds on the construction strategies and application prospects of TNBC organoids, with an outlook on their potential in individualized therapy.