Molecular identification of causative genetic and epigenetic alterations that induce and promote colorectal cancer

目前用于研究结直肠癌的大多数小鼠模型有两个缺陷。首先，他们倾向于关注小肠癌，而不是结直肠癌。值得注意的是，在人类的胃肠道癌症中，小肠癌只占少数。第二个问题是，引入老鼠体内的遗传损伤主要存在于整个发育过程中的所有细胞中。这不能很好地反映基因变化的随机性，而基因变化是结肠癌可能原因的基础。因此，我们建议从基因上设计出独特的小鼠模型，专注于结肠癌，以最接近地复制人类疾病的情况。然后，这些模型将可供其他人和我们开发和测试预防和/或治疗结直肠癌的疗法，这些疗法最终将用于患者。

The majority of mouse models currently employed to study colorectal cancer have two failings. The first is that they tend to focus on small intestinal cancers rather than colorectal cancers. It is important to note that small intestinal cancers are in the minority of gastrointestinal cancers in humans. The second problem is that the genetic lesions introduced into mice are mostly in all cells throughout development. This is a poor representation of the random nature of genetic changes that underpin the probable cause of colon cancer. We therefore propose to genetically engineer unique mouse models that focus on colon cancer to most closely replicate the situation in human disease. These models will then be available to others and us to develop and test therapies to prevent and-or treat colorectal cancer that will ultimately be used in patients.