Mcilhatton Michael A, Boivin Gregory P, Groden Joanna
Department of Cancer Biology and Genetics, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA.
Department of Pathology, Boonshoft School of Medicine, Wright State University, Health Sciences Building 053, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.
Biomed Res Int. 2016;2016:1414383. doi: 10.1155/2016/1414383. Epub 2016 Jun 20.
Technical and biological innovations have enabled the development of more sophisticated and focused murine models that increasingly recapitulate the complex pathologies of human diseases, in particular cancer. Mouse models provide excellent in vivo systems for deciphering the intricacies of cancer biology within the context of precise experimental settings. They present biologically relevant, adaptable platforms that are amenable to continual improvement and refinement. We discuss how recent advances in our understanding of tumorigenesis and the underlying deficiencies of DNA repair mechanisms that drive it have been informed by using genetically engineered mice to create defined, well-characterized models of human colorectal cancer. In particular, we focus on how mechanisms of DNA repair can be manipulated precisely to create in vivo models whereby the underlying processes of tumorigenesis are accelerated or attenuated, dependent on the composite alleles carried by the mouse model. Such models have evolved to the stage where they now reflect the initiation and progression of sporadic cancers. The review is focused on mouse models of colorectal cancer and how insights from these models have been instrumental in shaping our understanding of the processes and potential therapies for this disease.
技术和生物学创新推动了更复杂、更具针对性的小鼠模型的发展，这些模型越来越能重现人类疾病，尤其是癌症的复杂病理。小鼠模型为在精确的实验环境中解读癌症生物学的复杂性提供了出色的体内系统。它们提供了具有生物学相关性、可适应的平台，易于不断改进和完善。我们讨论了利用基因工程小鼠创建明确、特征良好的人类结直肠癌模型，如何为我们对肿瘤发生的最新认识以及驱动肿瘤发生的DNA修复机制的潜在缺陷提供信息。特别是，我们关注如何精确操纵DNA修复机制，以创建体内模型，根据小鼠模型携带的复合等位基因，加速或减弱肿瘤发生的潜在过程。这类模型已经发展到现在能够反映散发性癌症的起始和进展阶段。本综述聚焦于结直肠癌的小鼠模型，以及这些模型所提供的见解如何有助于我们理解该疾病的发病过程和潜在治疗方法。
