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

Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases.
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DOI:
10.1002/advs.202304460
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发表时间:
2024-01
期刊:
影响因子:
15.1
通讯作者:
Mao, Yilei
Mao, Yilei
中科院分区:
材料科学1区
文献类型:
--
作者:
Sun, Hang;Sun, Lejia;Ke, Xindi;Liu, Lijuan;Li, Changcan;Jin, Bao;Wang, Peipei;Jiang, Zhuoran;Zhao, Hong;Yang, Zhiying;Sun, Yongliang;Liu, Jianmei;Wang, Yan;Sun, Minghao;Pang, Mingchang;Wang, Yinhan;Wu, Bin;Zhao, Haitao;Sang, Xinting;Xing, Baocai;Yang, Huayu;Huang, Pengyu;Mao, Yilei

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由于肿瘤的异质性,准确预测结直肠癌(CRC)和结直肠癌肝转移(CRLM)对个性化化疗反应的方法仍然有限。本研究介绍了一种创新的患者来源的CRC和CRLM肿瘤模型,用于临床前研究,利用3d生物打印(3DP)技术。通过应用患者源性原发肿瘤细胞和生物墨水3D生物打印技术,实现了CRC/CRLM体外均匀3D模型的高效构建。基因组学和组织学分析证实,CRC/CRLM 3DP肿瘤模型有效地保留了亲代肿瘤生物标志物和突变谱。评估化疗药物敏感性的体外试验显示,在3DP CRC/CRLM模型中,化疗反应存在实质性的肿瘤异质性。此外,在CRLM 3DP模型中,药物反应与新辅助化疗的临床结果之间存在明显的强相关性。这些发现表明,患者衍生的3DP癌症模型在CRC/CRLM的精确化疗预测和临床前研究中具有重要的应用潜力。该研究展示了患者来源的结肠直肠癌及其肝转移的3D生物打印模型的建立。这些模型高度保留了亲本肿瘤生物标志物和突变谱,揭示了实质性的异质性。至关重要的是,药物测试与临床反应密切相关,这凸显了3D生物打印肿瘤模型作为个性化癌症治疗的临床前平台的巨大潜力。
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. The study showcases the establishment of patient‐derived 3D bioprinting models for colorectal cancer and its liver metastases. These models highly retain parent tumor biomarkers and mutation profiles, revealing substantial heterogeneity. Crucially, drug testing correlates strongly with clinical response, highlighting the great potential of 3D bioprinting tumor model as a preclinical platform for personalized cancer therapy.
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