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Mouse Models of RAS-Induced Tumors and Developmental Disorders

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Ras Superfamily Small G Proteins: Biology and Mechanisms 1

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Abstract

RAS oncogenes have been implicated in about one quarter of all human tumors including some of the cancers with worse prognosis such as lung adenocarcinoma, colorectal carcinoma, pancreatic ductal adenocarcinoma, and metastatic melanoma. In spite of the significant amount of knowledge accumulated over the last three decades regarding the molecular mechanisms by which RAS oncogenes induce malignant transformation, to date there are no efficacious therapies to selectively treat tumors carrying RAS mutations. One of the shortcomings in RAS research has been the lack of suitable experimental systems to study how RAS oncogenes induce cancer in an in vivo setting. The advent of sophisticated gene-targeting technologies are now making it possible to design mouse models of cancer that faithfully recapitulate the anatomo-pathological changes characteristic of those human tumors induced by RAS oncogenes. More recently, germline mutations in the three RAS loci have been found to be responsible for a series of developmental disorders known as RASopathies. Modeling these syndromes in mice should also help to understand the molecular events responsible for the developmental defects present in these human patients. This chapter summarizes those genetically engineered mouse models more frequently utilized to study RAS-induced tumors and developmental defects in an experimental setting. These mouse models should provide valuable experimental tools to identify molecular targets whose inhibition may open therapeutic avenues in the clinic, in a not too distant future.

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Acknowledgments

Work was supported by grants from the European Research Council (ERC-AG/250297-RAS AHEAD), the EU-Framework Programme (HEALTH-2010-260791), and the Spanish Ministry of Economy and Competitiveness (SAF2011-30173) to MB and grants from Fondo de Investigación Sanitaria (PI042124, PI08-1623, PI11-02529), Autonomous Community of Madrid (GR/SAL/0349/2004), and Fundación Ramón Areces (FRA 01-09-001) to CG.

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  1. Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain

    Carmen Guerra & Mariano Barbacid

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  1. Carmen Guerra
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Correspondence to Carmen Guerra or Mariano Barbacid .

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  1. Max-Planck-Institute of Molecular Physiology, Dortmund, Nordrhein-Westfalen, Germany

    Alfred Wittinghofer

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Guerra, C., Barbacid, M. (2014). Mouse Models of RAS-Induced Tumors and Developmental Disorders. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1806-1_10

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