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Targeting downstream effectors of Wnt signaling in colorectal cancer

Objectif

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 of
Apc 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.

Appel à propositions

ERC-2012-StG_20111109
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Régime de financement

ERC-SG - ERC Starting Grant

Institution d’accueil

BEATSON INSTITUTE FOR CANCER RESEARCH LBG
Adresse
Switchback Road Garscube Estate
G61 1BD Bearsden
United Kingdom

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Type d’activité
Research Organisations
Contact administratif
Peter Winckles (Mr.)
Chercheur principal
Owen James Sansom (Prof.)
Contribution de l’UE
€ 1 499 044,80

Bénéficiaires (1)

BEATSON INSTITUTE FOR CANCER RESEARCH LBG
United Kingdom
Contribution de l’UE
€ 1 499 044,80
Adresse
Switchback Road Garscube Estate
G61 1BD Bearsden

Voir sur la carte

Type d’activité
Research Organisations
Contact administratif
Peter Winckles (Mr.)
Chercheur principal
Owen James Sansom (Prof.)