Hayakawa Yoshihiro, Kawada Manabu, Nishikawa Hiroyoshi, Ochiya Takahiro, Saya Hideyuki, Seimiya Hiroyuki, Yao Ryoji, Hayashi Masahiro, Kai Chieko, Matsuda Akira, Naoe Tomoki, Ohtsu Atsushi, Okazaki Taku, Saji Hideo, Sata Masataka, Sugimura Haruhiko, Sugiyama Yuichi, Toi Masakazu, Irimura Tatsuro
Subcommittee on Non-clinical Studies, The Science Board to the Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
Division of Pathogenic Biochemistry, Department of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Cancer Sci. 2016 Feb;107(2):189-202. doi: 10.1111/cas.12857.
Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.
在肿瘤药物研发的每个阶段，非临床研究都是必要的。人们已经开发了许多实验性癌症模型来研究致癌作用、癌症进展、转移以及癌症生物学的其他方面，结果证明这些模型在肿瘤药物的疗效评估和安全性预测中很有用。虽然癌细胞生长和进展起始阶段基因变化的多样性和参与程度已被广泛接受，但宿主细胞、组织微环境和免疫系统在癌症中也发挥重要作用这一点已变得越来越明显。因此，用于开发肿瘤药物的方法应根据我们对癌症认识的进展不断修订。在本综述中，我们广泛总结了这些模型的有效应用、它们的优缺点、目前用于肿瘤药物研发和评估的模型的评估范围及局限性。
