TRRAP & BRAIN CANCER

Targeted inhibition of TRRAP as a strategy against aggressive brain cancer

Coordinatore	UNIVERSITY OF LEEDS    more  Organization address address: WOODHOUSE LANE city: LEEDS postcode: LS2 9JT contact info Titolo: Mr. Nome: Martin Cognome: Hamilton Email: send email Telefono: +44 113 343 4090
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-CIG
Funding Scheme	MC-CIG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-03-01   -   2016-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY OF LEEDS  Organization address address: WOODHOUSE LANE city: LEEDS postcode: LS2 9JT contact info Titolo: Mr. Nome: Martin Cognome: Hamilton Email: send email Telefono: +44 113 343 4090	UK (LEEDS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Patients with aggressive brain cancer have a very poor prognosis with an average life expectancy of only ~12 to 17 months. High grade brain tumors are extremely difficult to treat due to tumor cell invasion, plus resistance of tumor cells to DNA-damaging therapy. This cellular aggressiveness within brain tumors has been attributed to a subpopulation of tumor cells that possess stem cells-like features. Unlike differentiated tumor cells, brain tumour stem cells (BTSCs) possess the ability to self-renew, to withstand DNA-damaging therapy, and to give rise to new tumor mass. Therefore, targeting BTSCs is expected to improve the efficiency of anti-brain cancer therapy. In particular, targeting pathways that sustain the undifferentiated state of BTSCs is a novel strategy to treat aggressive brain tumors. However, this approach is hampered by a poor understanding of appropriate targets promoting the BTSC phenotype. Recently, we have demonstrated that the adapter protein TRRAP maintains BTSCs in an undifferentiated and highly tumorigenic state. Consistently, elevated expression of TRRAP in human brain tumors has a strong negative effect on patient survival. Therefore, we aim to provide a basis toward the development of an effective therapeutic strategy against the malignant function of TRRAP in BTSCs. To this end, we will use our established BTSC assay system and BTSC in vivo models in combination with differential proteomics to characterize TRRAP protein domains and TRRAP-protein interactions that critically promote the BTSC phenotype. Moreover, we will investigate the role of TRRAP during brain tumor invasion and potential additive effects between DNA-damaging therapy and inhibition of TRRAP function in vivo. Overall, these interrelated approaches will validate TRRAP as a brain tumor target. Ultimately, we hope to reveal and exploit the Achilles’ heel of TRRAP-dependent tumorigenesis for developing a targeted therapeutic strategy against BTSC-driven brain tumors.'