THESEUS
Tumour Heterogeneity and Somatic Evolution of Unstable cancer genomes
| Coordinatore | THE FRANCIS CRICK INSTITUTE LIMITED
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 1˙999˙940 € |
| EC contributo | 1˙999˙940 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2013-CoG |
| Funding Scheme | ERC-CG |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-06-01 - 2019-05-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
UK (LONDON) | beneficiary | 854˙502.40 |
| 2 |
CANCER RESEARCH UK
Organization address
address: ST JOHN STREET 407 ANGEL BUILDING contact info |
UK (LONDON) | beneficiary | 0.00 |
| 3 |
THE FRANCIS CRICK INSTITUTE LIMITED
Organization address
address: 215 Euston Road, Gibbs Building contact info |
UK (LONDON) | hostInstitution | 1˙145˙438.30 |
| 4 |
THE FRANCIS CRICK INSTITUTE LIMITED
Organization address
address: 215 Euston Road, Gibbs Building contact info |
UK (LONDON) | hostInstitution | 1˙145˙438.30 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (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'