RASTARGET
Targeting RAS oncogene addiction
| 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 | 2˙496˙221 € |
| EC contributo | 2˙496˙221 € |
| 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-2012-ADG_20120314 |
| Funding Scheme | ERC-AG |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-05-01 - 2018-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
CANCER RESEARCH UK
Organization address
address: ST JOHN STREET 407 ANGEL BUILDING contact info |
UK (LONDON) | beneficiary | 0.00 |
| 2 |
THE FRANCIS CRICK INSTITUTE LIMITED
Organization address
address: 215 Euston Road, Gibbs Building contact info |
UK (LONDON) | hostInstitution | 2˙496˙221.00 |
| 3 |
THE FRANCIS CRICK INSTITUTE LIMITED
Organization address
address: 215 Euston Road, Gibbs Building contact info |
UK (LONDON) | hostInstitution | 2˙496˙221.00 |
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Obiettivo del progetto (Objective)
'Lung cancer is the most common type of malignant tumour worldwide and the leading cause of cancer-related death (335,000 deaths per year in Europe). The KRAS oncogene is frequently activated by point mutation in human lung cancer and mutations in the RAS family oncogenes are responsible for driving some 20% of all human malignancies. Most cell lines from RAS mutant tumours remain “oncogene addicted” to continued RAS function. There is therefore a pressing need to develop cancer therapies that target RAS. To date it has proven impossible to target the RAS proteins directly and it is unclear whether combined targeting of downstream pathways that RAS controls will prove effective. We have previously probed the unique vulnerabilities of RAS mutant cancer cells using synthetic lethal genome-wide screening approaches. This has led to the identification of a transcriptional programme controlled by GATA2 that is selectively essential for RAS mutant lung cancer cell survival. Deletion of GATA2 leads to dramatic regression of RAS induced in lung cancer in mouse models. Although GATA2 itself is likely to be undruggable, combined suppression of two GATA2 regulated pathways, ROCK and the proteasome, with clinically approved inhibitors causes marked tumour clearance. We propose to investigate the ability of these promising targeting strategies to impact on various RAS induced cancers and also to investigate mechanistic aspects of this dependency on GATA2 function. We will test the effect of GATA2 deletion or ROCK/proteasome combination therapy on RAS mutant tumour maintenance in the setting of p53 loss, both in lung and pancreatic cancer. In addition, we will determine the mechanisms involved in the dependency of RAS mutant cancers on these pathways in vivo, including investigating effects on the interaction of the tumour with host tissues, with a view to finding improved means of targeting these tumours and avoiding the development of resistance to these therapies.'