Objective
DNA damage has been implicated as a causal factor of cancer development and is thought to contribute to aging. The effect of DNA damage both in cancer and aging becomes particularly apparent in patients that are defective in nucleotide excision repair (NER). NER comprises two distinct branches that differ in the initial damage recognition and lead to distinct clinical outcomes. Global genome (GG) NER recognizes damages throughout the genome, whereas transcription-coupled repair (TCR) specifically removes damage during transcription. GG-NER deficiencies lead to the skin cancer susceptibility syndromes xeroderma pigmentosum (XP) whereas TCR deficiencies lead to progeroid conditions Cockayne syndrome (CS), trichothiodystrophy (TTD) and XPF-ERCC1 progeria (XFE). Recently, we have identified specific cellular response programs to persistent transcription-blocking lesions. We showed that persistent transcription-blocking lesions lead to attenuation of IGF-1R and GHR resulting in cellular IGF-1 resistance. IGF-1R and GHR are central regulators of somatic growth and their attenuation leads to extended longevity and stress resistance. IGF-1R has been shown to act as oncogene and pharmaceutical interventions targeting IGF-1R are in advanced clinical trials for cancer treatment. We have found that, in contrast to cells from tumor prone XP mice, primary cells from progeroid CS or XFE mouse models induce a prolonged IGF-1R and GHR attenuation. We proposed that somatotropic attenuation might be the critical determent of the progeroid but tumor free outcome of TCR deficiencies and the tumor prone outcome of GG-NER deficiencies. In this proposal we aim at investigating genetic interactions of skin cancer models of XP and IGF-1R knockout mutants. We thus aim at investigating tumor suppression strategies in skin cancer models to gain novel insights into the biology of skin cancer development and the biology of aging as well as giving rise to novel anti-cancer treatment strategies.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine oncology skin cancer
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics nucleotides
- natural sciences biological sciences genetics genomes
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Programme(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-ERG-2008
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Funding Scheme
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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
50931 KOLN
Germany
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.