Shen Suya, Liu Bing, Guan Wenyan, Liu Ziyao, Han Yuqing, Hu Yingzhe, Chen Yiqiang, Liu Siyuan, He Jian, Li Zhiwen, Tang Weifeng, Zhang Pengju, Ren Wei, Qiu Yudong, Zheng Hongping, Li Jingjing
Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
J Transl Med. 2024 Dec 31;22(1):1168. doi: 10.1186/s12967-024-05967-1.
Patient-derived organoids (PDOs) represent a promising approach for replicating the characteristics of original tumors and facilitating drug testing for personalized treatments across diverse cancer types. However, clinical evidence regarding their application to esophageal cancer remains limited. This study aims to evaluate the efficacy of implementing PDOs in clinical practice to benefit patients with esophageal squamous cell carcinoma (ESCC).
Fresh surgical biopsies were obtained from patients with esophageal cancer for the establishment of PDOs. These PDOs were subsequently characterized through histological analysis. A customized drug panel, based on standard-of-care chemotherapy regimens, was applied to the PDOs. The resulting drug sensitivity profiles were then correlated with the clinical responses observed in individual patients undergoing actual treatment.
A total of 34 PDOs were successfully established with a 61.8% success rate. The classification method based on chemotherapy sensitivity closely corresponded to clinical responses. The paclitaxel plus cisplatin (TP)-sensitive group demonstrated significantly longer progression-free survival (PFS) compared to the resistant groups, Hazard ratio (HR), 5.12; 95% confidence intervals (CI 0.58-44.71; p < 0.05), thus illustrating the potential of this approach for guiding personalized treatment strategies.
Organoid biobanks were established across multiple institutes to facilitate PDOs-based functional precision medicine. The findings demonstrate that this framework offers robust predictive value in clinical settings, enhances precision therapeutics, and advances drug discovery for esophageal cancer.
患者来源的类器官（PDO）是一种很有前景的方法，可用于复制原发肿瘤的特征，并促进针对多种癌症类型的个性化治疗进行药物测试。然而，关于其在食管癌中的应用的临床证据仍然有限。本研究旨在评估在临床实践中应用PDO以造福食管鳞状细胞癌（ESCC）患者的疗效。
从食管癌患者获取新鲜手术活检组织以建立PDO。随后通过组织学分析对这些PDO进行表征。基于标准护理化疗方案应用定制的药物组合对PDO进行检测。然后将所得的药物敏感性谱与接受实际治疗的个体患者中观察到的临床反应相关联。
共成功建立了34个PDO，成功率为61.8%。基于化疗敏感性的分类方法与临床反应密切对应。与耐药组相比，紫杉醇加顺铂（TP）敏感组的无进展生存期（PFS）显著更长，风险比（HR）为5.12；95%置信区间（CI 0.58 - 44.71；p < 0.05），从而说明了这种方法在指导个性化治疗策略方面的潜力。
跨多个机构建立了类器官生物样本库，以促进基于PDO的功能精准医学。研究结果表明，该框架在临床环境中具有强大的预测价值，可提高精准治疗水平，并推动食管癌的药物发现。
