Marin Jose J G, Herraez Elisa, Lozano Elisa, Macias Rocio I R, Briz Oscar
Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, IBSAL, 37007 Salamanca, Spain.
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain.
Cancers (Basel). 2019 Oct 29;11(11):1677. doi: 10.3390/cancers11111677.
The lack of response to pharmacological treatment constitutes a substantial limitation in the handling of patients with primary liver cancers (PLCs). The existence of active mechanisms of chemoresistance (MOCs) in hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma hampers the usefulness of chemotherapy. A better understanding of MOCs is needed to develop strategies able to overcome drug refractoriness in PLCs. With this aim, several experimental models are commonly used. These include in vitro cell-free assays using subcellular systems; studies with primary cell cultures; cancer cell lines or heterologous expression systems; multicellular models, such as spheroids and organoids; and a variety of in vivo models in rodents, such as subcutaneous and orthotopic tumor xenografts or chemically or genetically induced liver carcinogenesis. Novel methods to perform programmed genomic edition and more efficient techniques to isolate circulating microvesicles offer new opportunities for establishing useful experimental tools for understanding the resistance to chemotherapy in PLCs. In the present review, using three criteria for information organization: (1) level of research; (2) type of MOC; and (3) type of PLC, we have summarized the advantages and limitations of the armamentarium available in the field of pharmacological investigation of PLC chemoresistance.
对药物治疗缺乏反应是原发性肝癌（PLC）患者治疗过程中的一个重大限制。肝细胞癌、胆管癌和肝母细胞瘤中存在的化学抗性活性机制（MOC）阻碍了化疗的有效性。需要更好地了解MOC，以制定能够克服PLC药物难治性的策略。为此，通常使用几种实验模型。这些模型包括使用亚细胞系统的体外无细胞分析；原代细胞培养研究；癌细胞系或异源表达系统；多细胞模型，如球体和类器官；以及多种啮齿动物体内模型，如皮下和原位肿瘤异种移植或化学或基因诱导的肝癌发生。进行程序性基因组编辑的新方法和分离循环微泡的更有效技术为建立用于理解PLC化疗抗性的有用实验工具提供了新机会。在本综述中，我们使用信息组织的三个标准：（1）研究水平；（2）MOC类型；（3）PLC类型，总结了PLC化学抗性药理研究领域现有工具的优缺点。
