Objetivo Colorectal cancer (CRC) is one of the most common cancers of the western world. The underlying initiating mutation for the majority of CRC is within the Adenomatous Polyposis Coli (Apc) gene. The APC protein performs an important role in controlling the levels of Wnt signalling by targeting beta-catenin for degradation. Loss of the APC protein leads to the activation of Wnt signaling target genes such as c-Myc which is required for phenotypes causes by Apc loss.However, despite the clear importance of APC loss and deregulated Wnt signalling, additional events are required for the development of CRC such as KRAS and P53 mutations.The impact of these changes on the development of CRC and response to therapy is not well understood. Furthermore, identification and testing of potential novel targets and therapies is hampered by lack of a preclinical model that faithfully recapitulates the course of the human disease.This proposal has two aims:1. Assess the impact of cooperating mutations with Apc and assess how they alter sensitivities ofApc deficient cells.2. Develop mouse models of invasive and metastatic colorectal cancer that recapitulate the human disease.We will use ‘state of the art’ methodologies to identify the changes in signaling output conferred by these cooperating mutations. Genetic mouse models of invasive and metastatic colorectal cancers will be generated through the acquisition of additional mutations and genomic instability.These studies will produce predictions on therapeutic combinations that will be tested in mouse models in vitro and in vivo that may identify new treatment regimens for patients with late stage CRC. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutation Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2012-StG_20111109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida BEATSON INSTITUTE FOR CANCER RESEARCH LBG Aportación de la UE € 1 499 044,80 Dirección SWITCHBACK ROAD GARSCUBE ESTATE G61 1BD Bearsden Reino Unido Ver en el mapa Región Scotland West Central Scotland East Dunbartonshire Tipo de actividad Research Organisations Contacto administrativo Peter Winckles (Mr.) Investigador principal Owen James Sansom (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo BEATSON INSTITUTE FOR CANCER RESEARCH LBG Reino Unido Aportación de la UE € 1 499 044,80 Dirección SWITCHBACK ROAD GARSCUBE ESTATE G61 1BD Bearsden Ver en el mapa Región Scotland West Central Scotland East Dunbartonshire Tipo de actividad Research Organisations Contacto administrativo Peter Winckles (Mr.) Investigador principal Owen James Sansom (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos