Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
J Cell Mol Med. 2024 May;28(9):e18374. doi: 10.1111/jcmm.18374.
The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.
大多数晚期乳腺癌表现出较强的侵袭性、异质性和耐药性，目前缺乏有效的治疗策略是癌症研究必须面对的主要挑战之一。因此，迫切需要开发一种可行的临床前模型来探索针对难治性乳腺癌的靶向治疗方法。我们从 17 名乳腺癌患者中建立了类器官生物库，并通过免疫组织化学（IHC）和下一代测序（NGS）对其进行了特征分析。此外，我们首次将患者来源的类器官（PDOs）与迷你患者来源的异种移植（Mini-PDXs）相结合，用于快速、精确地筛选药物敏感性。我们证实乳腺癌类器官是体外高保真的三维（3D）模型，可重现原始肿瘤的组织学和遗传特征。此外，对于一名接受过多重预处理的晚期耐药性乳腺癌患者，我们结合了 PDO 和 Mini-PDX 模型，以确定对该患者有效的治疗药物组合，即 alpelisib + fulvestrant。在类器官的药物敏感性实验中，我们观察到 PI3K/AKT/mTOR 信号通路和雌激素受体（ER）蛋白表达水平的变化，这进一步验证了筛选结果的可靠性。我们的研究表明，PDO 与 mini-PDX 模型相结合提供了一种快速、精确的药物筛选平台，有望为个性化医疗提供帮助，改善患者的治疗效果，并满足晚期乳腺癌有效治疗方法的迫切需求。
