Objective
Acquisition of the hallmark capability for invasion and in turn metastasis is for most human cancers the defining event in progression to life threatening disease. Its determinants are remarkably complex. Genetically engineered mice can model human cancers, with tumors arising in specific organs, reflecting onco-genomic and histopathological features of particular tumor types. This project will use four mouse models to characterize newly implicated determinants of invasive tumor growth. We have observed that genetic polymorphisms can govern predisposition to invasive cancer. Additionally, therapeutic targeting of another hallmark capability – tumor angiogenesis – has revealed adaptive resistance, whereby late-stage tumors, faced with the inability to grow en masse supported by angiogenesis, switch instead to grow diffusively, by invading adjacent tissue; this phenomenon may underlay the limited benefit seen with anti-angiogenic therapies in the clinic. There are three interconnected goals:
(1) Polymorphic regulation of tumor invasion. We will investigate the mechanisms and functional importance of candidate genes resident within a genetic modifier locus on mouse Chr 17 that can alternatively suppress or facilitate invasive tumor growth dependent on constitutional genetic background.
(2) Adaptive induction of invasion. We will elucidate the determinants of the invasive growth capability that is induced in response to potent inhibition of angiogenesis.
(3) Testing mechanism-based therapeutic co-targeting of the capabilities for invasion and angiogenesis.
We will use functional genetic, genomic profiling, and pharmacological approaches to assess these two new modes of regulating invasive growth, and then apply the knowledge in preclinical trials aiming to lay the groundwork for future clinical trials in which these intersecting hallmark capabilities are coordinately disrupted, with promise for more enduring therapeutic responses and benefit to cancer patients.
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.
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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.
ERC-2012-ADG_20120314
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.
Host institution
1015 LAUSANNE
Switzerland
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.