Objective
Summary
The majority of metastastic solid tumours remain incurable. In-depth analysis of tumour genomes is revealing evidence for branched evolution and cancer subclonal spatial and temporal intratumour heterogeneity (ITH). Drivers of ITH such as chromosomal instability (CIN) are associated with drug resistance and poor clinical outcome. However, despite increasing knowledge of tumour diversity, there is limited insight into the mechanisms driving genomic instability and ITH or the processes that shape cancer genome evolution over time and space. Many animal tumour models fail to recapitulate patterns of genomic instability witnessed in human tumours, limiting insight into the forces that shape tumour evolution in vivo. We have found evidence for parallel subclonal evolution, resulting in the same gene or signal transduction pathway being subject to distinct inactivating or activating somatic events in different regions of the same tumour (Gerlinger NEJM 2012). These data suggest that in-depth analysis of tumour evolution may help define routes through which tumours must progress, offering opportunities for novel therapeutic approaches. We will develop new animal models of ITH, by developing knock-out strains for two suppressors of replication stress and CIN, recently identified in our laboratory (Burrell Nature 2013). These models will be used to study cancer evolution in order to decipher the impact of selection pressures, such as DNA damaging agents and cancer cytotoxics, on genomic complexity and diversity in emergent resistant subclones. In addition, through combined cancer informatics and functional genomics approaches we aim to identify novel mechanisms driving tumour heterogeneity and biological processes that permit the propagation of heterogeneous cells using novel transposon based approaches. Developments in this proposal may lead to new insight into the two forces underpinning cancer evolution and therapeutic failure, diversity and selection
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.
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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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-2013-CoG
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
NW1 1AT London
United Kingdom
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.