Caviglia Jorge Matias, Schwabe Robert F
Department of Medicine, Columbia University, Russ Berrie Pavilion, Room 415, 1150 St. Nicholas Ave, New York, NY, 10032, USA.
Methods Mol Biol. 2015;1267:165-83. doi: 10.1007/978-1-4939-2297-0_8.
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and the third leading cause of cancer mortality. The great majority of patients are not eligible for curative therapies, and therapeutic approaches for advanced disease show only limited efficacy. Difficulties to treat HCC are due to the heterogenous genetic alterations of HCC, profound alterations in the hepatic microenvironment, and incomplete understanding of HCC biology. Mouse models of HCC will be helpful to improve our understanding of HCC biology, the contributions of the specific pathways and genetic alterations to carcinogenesis. In addition, mouse models of HCC may contribute to elucidate the role of the tumor microenvironment, and serve as models for preclinical studies. As no single mouse model is appropriate to study all of the above, we discuss key features and limitations of commonly used models. Furthermore, we provide detailed protocols for select models, in which HCC is induced genetically, chemically or by transplantation of tumor cells.
肝细胞癌(HCC)是全球第六大常见癌症,也是癌症死亡的第三大主要原因。绝大多数患者不符合根治性治疗的条件,晚期疾病的治疗方法疗效有限。HCC难以治疗的原因在于其基因改变的异质性、肝脏微环境的深刻改变以及对HCC生物学的不完全理解。HCC小鼠模型将有助于提高我们对HCC生物学的理解,以及特定途径和基因改变在致癌过程中的作用。此外,HCC小鼠模型可能有助于阐明肿瘤微环境的作用,并作为临床前研究的模型。由于没有单一的小鼠模型适合研究上述所有内容,我们讨论了常用模型的关键特征和局限性。此外,我们提供了选定模型的详细方案,其中HCC是通过基因、化学方法或肿瘤细胞移植诱导产生的。