Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

晚期结直肠癌的治疗方案更为复杂。本研究构建了晚期结直肠癌患者来源类器官（patient-derived tumoroids）的活体生物样本库（living biobank），并展示了此类类器官可用于体外模拟肿瘤行为，同时为类器官可作为化疗期间的预测平台以识别化疗应答提供了更多证据。本研究对结直肠癌类器官开展了形态学、组织学及基因组学特征分析。进一步，本研究使用不同药物处理结直肠癌类器官，通过CellTiter-Glo 3D细胞活力检测试剂盒检测细胞活性以评估药物敏感性。随后将类器官的药物敏感性数据与患者临床结局进行比对。研究结果显示，类器官可复刻原始肿瘤的组织学特征，且类器官的基因组谱与匹配的原发肿瘤具有高度相似性。类器官的各治疗谱分析所得的剂量反应曲线、曲线下面积及肿瘤抑制率均表现出显著多样性，且类器官敏感性数据与配对患者临床结局的匹配率达88.24%。类器官各治疗参数的肿瘤抑制率与对应患者的无进展生存期（progression-free survival）呈正相关，而各治疗参数的曲线下面积则与患者无进展生存期呈负相关。综上，本研究构建了晚期结直肠癌患者来源类器官的活体生物样本库，并证实类器官具备预测晚期结直肠癌患者化疗临床应答的巨大潜力。