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KRAS小鼠模型:对携带KRAS突变的癌症进行建模。

KRAS Mouse Models: Modeling Cancer Harboring KRAS Mutations.

作者信息

O'Hagan Rónán C, Heyer Joerg

机构信息

AVEO Pharmaceuticals, Cambridge, MA, USA.

出版信息

Genes Cancer. 2011 Mar;2(3):335-43. doi: 10.1177/1947601911408080.

Abstract

KRAS is a potent oncogene and is mutated in about 30% of all human cancers. However, the biological context of KRAS-dependent oncogenesis is poorly understood. Genetically engineered mouse models of cancer provide invaluable tools to study the oncogenic process, and insights from KRAS-driven models have significantly increased our understanding of the genetic, cellular, and tissue contexts in which KRAS is competent for oncogenesis. Moreover, variation among tumors arising in mouse models can provide insight into the mechanisms underlying response or resistance to therapy in KRAS-dependent cancers. Hence, it is essential that models of KRAS-driven cancers accurately reflect the genetics of human tumors and recapitulate the complex tumor-stromal intercommunication that is manifest in human cancers. Here, we highlight the progress made in modeling KRAS-dependent cancers and the impact that these models have had on our understanding of cancer biology. In particular, the development of models that recapitulate the complex biology of human cancers enables translational insights into mechanisms of therapeutic intervention in KRAS-dependent cancers.

摘要

KRAS是一种强大的致癌基因,在约30%的人类癌症中发生突变。然而,KRAS依赖性肿瘤发生的生物学背景却知之甚少。癌症的基因工程小鼠模型为研究致癌过程提供了宝贵的工具,来自KRAS驱动模型的见解显著增进了我们对KRAS能够发挥致癌作用的遗传、细胞和组织背景的理解。此外,小鼠模型中出现的肿瘤之间的差异可以为KRAS依赖性癌症对治疗产生反应或耐药的潜在机制提供见解。因此,至关重要的是,KRAS驱动癌症的模型要准确反映人类肿瘤的遗传学特征,并重现人类癌症中明显存在的复杂肿瘤-基质相互作用。在这里,我们强调了在构建KRAS依赖性癌症模型方面取得的进展以及这些模型对我们理解癌症生物学所产生的影响。特别是,能够重现人类癌症复杂生物学特征的模型的开发,有助于对KRAS依赖性癌症的治疗干预机制进行转化性研究。

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