He Xingfeng, Jiang Yan, Zhang Long, Li Yaqi, Hu Xiang, Hua Guoqiang, Cai Sanjun, Mo Shaobo, Peng Junjie
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Bioeng Biotechnol. 2023 May 22;11:1190637. doi: 10.3389/fbioe.2023.1190637. eCollection 2023.
Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy. In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids. The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients. In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC.
大多数晚期结直肠癌具有侵袭性，且缺乏选择合适抗癌方案的有效方法。患者来源的类器官（PDO）已成为模拟癌症治疗临床反应的临床前平台。在本研究中，我们成功构建了一个生物样本库，其中包含42个源自转移性结直肠癌患者原发灶和转移灶的类器官。肿瘤组织取自接受原发灶或转移灶手术切除的患者，然后用于建立PDO。进行免疫组织化学（IHC）和药物敏感性分析以分析这些类器官的特性。转移性结直肠癌类器官成功建立，成功率为80%。PDO保持了其亲本肿瘤的遗传和表型异质性。使用药物敏感性分析确定了转移性结直肠癌类器官对5-氟尿嘧啶（5-FU）、奥沙利铂和伊立替康（CPT11）的IC50值。体外化学敏感性数据揭示了PDO在预测转移性结直肠癌患者化疗反应和临床结果的临床应用中的潜在价值。总之，PDO模型是体外评估患者特异性药物敏感性的有效平台，可指导晚期结直肠癌患者的个性化治疗决策。
