Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China.
Department of General Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Adv Sci (Weinh). 2024 Jan;11(2):e2304460. doi: 10.1002/advs.202304460. Epub 2023 Nov 16.
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.
由于肿瘤异质性，能够准确预测结直肠癌（CRC）和结直肠癌肝转移（CRLM）对个体化化疗反应的方法仍然有限。本研究引入了一种创新的患者衍生的 CRC 和 CRLM 肿瘤模型，用于临床前研究，利用 3d 生物打印（3DP）技术。通过应用患者衍生的原代肿瘤细胞和生物墨水的 3D 生物打印，高效构建了同质的 CRC/CRLM 体外 3D 模型。基因组和组织学分析证实，CRC/CRLM 3DP 肿瘤模型有效地保留了亲本肿瘤的生物标志物和突变特征。体外化疗药物敏感性测试表明，3DP CRC/CRLM 模型中的化疗反应存在显著的肿瘤异质性。此外，在 CRLM 3DP 模型中的药物反应与新辅助化疗的临床结果之间存在明显的相关性。这些发现表明，患者衍生的 3DP 癌症模型在 CRC/CRLM 的精准化疗预测和临床前研究中有很大的应用潜力。
