Objective
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death and has the lowest survival rate of all major cancers (3-5%). Despite our advanced understanding of disease pathology and underlying genetics, there are no effective chemotherapeutic or targeted treatment options, and the median survival time remains unchanged at only 6 months. PDAC arises from complex and heterogeneous genetic aberrations, which in a single case typically involve >50 genes. Besides four hallmark mutations affecting KRAS, TP53, CDKN2A and SMAD4, aberrations of the chromatin regulatory machinery are common in PDAC. Chromatin-associated genes are particularly attractive as drug targets, since resulting epigenetic aberrations are reversible and often amendable to drug-based modulation. However, the mechanistic role of chromatin aberrations, as well as their potential as therapeutic targets have not been explored in PDAC. In order to accelerate the search for more effective therapies for this devastating disease, this project will combine genetically engineered PDAC mouse models, multiplexed RNAi screening and advanced in vivo RNAi technologies to systematically analyze chromatin-regulatory genes in tumorigenesis and maintenance of PDAC. As tractable experimental system for in vivo RNAi studies, I will generate a Tet-on competent PDAC mouse model based on endogenous KrasG12D and homozygous loss of Trp53. Following its characterization, the model will be employed in multiplexed in vitro and in vivo RNAi screens using a new chromatin shRNA library. Selected hits will be functionally characterized using innovative in vivo RNAi approaches. Overall, these studies aim to advance our mechanistic understanding of chromatin (dys)regulation in PDAC, identify new target molecules for the development of more effective therapeutic, and establish a powerful in vivo system that is generally applicable for the pre-clinical evaluation of targeted therapies in PDAC.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine oncology pancreatic cancer
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IEF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1030 Wien
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.