Lu Jia-Huan, Wang Yun, Meng Qi, Zeng Zhao-Lei
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center;
J Vis Exp. 2019 Jul 19(149). doi: 10.3791/59871.
The use of preclinical models to advance our understanding of tumor biology and investigate the efficacy of therapeutic agents is key to cancer research. Although there are many established gastric cancer cell lines and many conventional transgenic mouse models for preclinical research, the disadvantages of these in vitro and in vivo models limit their applications. Because the characteristics of these models have changed in culture, they no longer model tumor heterogeneity, and their responses have not been able to predict responses in humans. Thus, alternative models that better represent tumor heterogeneity are being developed. Patient-derived xenograft (PDX) models preserve the histologic appearance of cancer cells, retain intratumoral heterogeneity, and better reflect the relevant human components of the tumor microenvironment. However, it usually takes 4-8 months to develop a PDX model, which is longer than the expected survival of many gastric patients. For this reason, establishing primary cancer cell lines may be an effective complementary method for drug response studies. The current protocol describes methods to establish PDX models and primary cancer cell lines from surgical gastric cancer samples. These methods provide a useful tool for drug development and cancer biology research.
利用临床前模型增进我们对肿瘤生物学的理解并研究治疗药物的疗效是癌症研究的关键。尽管有许多已建立的胃癌细胞系以及许多用于临床前研究的传统转基因小鼠模型，但这些体外和体内模型的缺点限制了它们的应用。由于这些模型的特性在培养过程中发生了变化，它们不再模拟肿瘤异质性，并且它们的反应无法预测人类的反应。因此，正在开发能更好地代表肿瘤异质性的替代模型。患者来源的异种移植（PDX）模型保留了癌细胞的组织学外观，保持了肿瘤内异质性，并能更好地反映肿瘤微环境中的相关人类成分。然而，建立一个PDX模型通常需要4至8个月，这比许多胃癌患者的预期生存期还要长。因此，建立原发性癌细胞系可能是药物反应研究的一种有效补充方法。本方案描述了从手术切除的胃癌样本中建立PDX模型和原发性癌细胞系的方法。这些方法为药物开发和癌症生物学研究提供了一个有用的工具。
