Chen Jie, Liu Liangquan, Yang Yunxu, Luo Jing, Liu Shengchun
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Breast Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
J Drug Target. 2025 Aug;33(7):1179-1189. doi: 10.1080/1061186X.2025.2473010. Epub 2025 Mar 13.
Malignant phyllodes tumours (MPT) of the breast are rare fibroepithelial neoplasms. It exhibits rapid growth, large size, and a high local recurrence rate.
In this study, we established novel patient-derived organoid (PDO) models from two primary MPT samples and conducted comprehensive genetic profiling and drug screening.
The PDO models faithfully recapped the histopathological and molecular features of the primary tumours, including stromal overgrowth, leaf-like projections, and the expression of key diagnostic markers. Drug testing revealed significant heterogeneity in response profiles to chemotherapeutic reagents between the two MPT-derived organoids, implying the importance of personalised drug testing. Next-generation sequencing analysis identified recurrent mutations in TP53, RB1, EGFR, ATM, and RECQL4, which correlated with the drug sensitivity profiles observed in the organoid models. Targeted therapeutic drugs, such as Abemaciclib (targeting the RB1 pathway) with an IC value of 1.744 µM, and Alflutinib Mesylate (targeting the EGFR pathway) with an IC value of 0.9150 µM, exhibited significant cytotoxic effects in the MPT2 organoid models.
This study highlights the novel application of PDOs for studying the molecular landscape of MPTs and identifying effective therapeutic targets, offering a promising platform for guiding personalised treatment strategies for this rare and challenging cancer.
乳腺恶性叶状肿瘤（MPT）是一种罕见的纤维上皮性肿瘤。它生长迅速、体积大且局部复发率高。
在本研究中，我们从两个原发性MPT样本建立了新型患者来源类器官（PDO）模型，并进行了全面的基因分析和药物筛选。
PDO模型忠实地重现了原发性肿瘤的组织病理学和分子特征，包括间质过度生长、叶状突起以及关键诊断标志物的表达。药物测试显示，两种源自MPT的类器官对化疗试剂的反应谱存在显著异质性，这意味着个性化药物测试的重要性。二代测序分析确定了TP53、RB1、EGFR、ATM和RECQL4中的复发性突变，这些突变与在类器官模型中观察到的药物敏感性谱相关。靶向治疗药物，如阿贝西利（靶向RB1通路），IC值为1.744µM，以及甲磺酸阿夫替尼（靶向EGFR通路），IC值为0.9150µM，在MPT2类器官模型中表现出显著的细胞毒性作用。
本研究突出了PDO在研究MPT分子格局和确定有效治疗靶点方面的新应用，为指导这种罕见且具有挑战性的癌症的个性化治疗策略提供了一个有前景的平台。
