Chair of Livestock Biotechnology, Technische Universität München, Liesel-Beckmann-Straße 1, 85354 Freising, Germany.
Transgenic Res. 2013 Aug;22(4):673-80. doi: 10.1007/s11248-013-9720-9. Epub 2013 Jun 8.
The molecular mechanisms underlying many human cancers are now reasonably well understood. The challenge now is to bridge the gap between laboratory and clinical oncology, so these accomplishments can be translated into practical benefits for human patients. While genetically modified mice have played a prominent role in basic research, they are less suitable for many preclinical studies. Other animals can provide important complementary resources to aid the development, validation and application of new medicines and procedures. Powerful methods of genetic engineering have now been extended to physiologically more relevant species, particularly the pig, opening the prospect of more representative, genetically defined, cancer models at human scale. We briefly review the field and outline our program to generate gene-targeted pigs carrying mutations in tumour suppressor genes and proto-oncogenes that replicate key lesions responsible for a variety of human cancers. We also highlight some important issues for the future development and usefulness of porcine cancer models.
许多人类癌症的分子机制现在已经得到了很好的理解。现在的挑战是弥合实验室肿瘤学和临床肿瘤学之间的差距,以便将这些成果转化为人类患者的实际利益。虽然基因修饰小鼠在基础研究中发挥了重要作用,但它们不太适合许多临床前研究。其他动物可以提供重要的补充资源,以帮助开发、验证和应用新药和程序。强大的基因工程方法现在已经扩展到更具生理相关性的物种,特别是猪,为人类规模的更具代表性、基因定义的癌症模型开辟了前景。我们简要回顾了这一领域,并概述了我们的计划,以生成携带肿瘤抑制基因和原癌基因突变的基因靶向猪,这些突变复制了导致各种人类癌症的关键病变。我们还强调了猪癌症模型未来发展和有用性的一些重要问题。