Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases

利用患者来源的结肠直肠癌及其肝转移 3D 生物打印模型预测临床精准化疗

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作者:Hang Sun, Lejia Sun, Xindi Ke, Lijuan Liu, Changcan Li, Bao Jin, Peipei Wang, Zhuoran Jiang, Hong Zhao, Zhiying Yang, Yongliang Sun, Jianmei Liu, Yan Wang, Minghao Sun, Mingchang Pang, Yinhan Wang, Bin Wu, Haitao Zhao, Xinting Sang, Baocai Xing, Huayu Yang, Pengyu Huang, Yilei Mao

Abstract

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

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