Cel 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. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutation Program(-y) 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) Temat(-y) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Zaproszenie do składania wniosków ERC-2012-StG_20111109 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca BEATSON INSTITUTE FOR CANCER RESEARCH LBG Wkład UE € 1 499 044,80 Adres SWITCHBACK ROAD GARSCUBE ESTATE G61 1BD Bearsden Zjednoczone Królestwo Zobacz na mapie Region Scotland West Central Scotland East Dunbartonshire Rodzaj działalności Research Organisations Kontakt administracyjny Peter Winckles (Mr.) Kierownik naukowy Owen James Sansom (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko BEATSON INSTITUTE FOR CANCER RESEARCH LBG Zjednoczone Królestwo Wkład UE € 1 499 044,80 Adres SWITCHBACK ROAD GARSCUBE ESTATE G61 1BD Bearsden Zobacz na mapie Region Scotland West Central Scotland East Dunbartonshire Rodzaj działalności Research Organisations Kontakt administracyjny Peter Winckles (Mr.) Kierownik naukowy Owen James Sansom (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych