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    Methods for identifying anti-cancer drug targets
    5.
    发明授权
    Methods for identifying anti-cancer drug targets 有权
    鉴定抗癌药物靶标的方法

    公开(公告)号：US06489127B1

    公开(公告)日：2002-12-03

    申请号：US09716661

    申请日：2000-11-20

    申请人： Geoffrey Duyk ,  Felix D. Karim

    发明人： Geoffrey Duyk ,  Felix D. Karim

    IPC分类号： G01N33567

    CPC分类号： C12N15/8509 ,  A01K67/0339 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2227/30 ,  A01K2227/703 ,  A01K2227/706 ,  A01K2267/0331 ,  A01K2267/0393 ,  C12N2800/30 ,  C12N2800/90 ,  C12N2830/008 ,  C12N2830/75 ,  C12N2830/85 ,  C12N2840/203

    摘要： Methods, transformation constructs, and transgenic animals for identifying anti-tumor agents and anti-tumor drug targets are described. The transformation constructs are used to generate transgenic animals that have altered expression of an oncogene or tumor suppressor gene in a target tissue that is dispensable for viability and reproduction. In some embodiments, the altered expression results in abnormal proliferation of the target tissue and normal proliferation in all other tissues. Anti-tumor drug targets can be identified by generating progeny of the transgenic animals that have mutations in various genes. Gene mutations that result in a specific reduction or killing of the target tissue are identified as possible anti-tumor drug targets and are further evaluated. Anti-tumor agents are identified that mimic the effect of the gene mutations that result in specific reduction of the target tissue. Alternatively, anti-tumor agents can be identified by administering various compounds directly to the transgenic animals, or their progeny, and selecting as putative therapeutic agents, compounds that result in target-tissue specific antiproliferation.

    摘要翻译： 描述了用于鉴定抗肿瘤剂和抗肿瘤药物靶标的方法，转化构建体和转基因动物。 转化构建体用于产生转基因动物，所述转基因动物已经改变了靶向组织中的致癌基因或肿瘤抑制基因的表达，其对生存力和繁殖是不必要的。 在一些实施方案中，改变的表达导致靶组织的异常增殖和所有其他组织中的正常增殖。 可以通过产生具有各种基因突变的转基因动物的后代来鉴定抗肿瘤药物靶标。 导致特异性还原或杀死靶组织的基因突变被鉴定为可能的抗肿瘤药物靶标，并进一步评估。 确定抗肿瘤剂，其模拟导致靶组织特异性还原的基因突变的作用。 或者，可通过将各种化合物直接施用于转基因动物或其后代，并选择导致靶组织特异性抗增殖的化合物来确定抗肿瘤剂。