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Predicting individual response and resistance to VEGFR/mTOR pathway therapeutic intervention using biomarkers discovered through tumour functional genomics

Objective

The strategic development of accurate biomarkers to predict response to therapy in cancer medicine will enhance clinical outcome and reduce the health economic impact of drug resistant disease. The PREDICT consortium will identify and validate predictive biomarkers for two drugs which have direct anti-tumour cell and anti-angiogenic activity and for which no established predictive biomarkers of tumour response exist: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mTOR pathway inhibitor. Renal cell carcinoma (RCC), a disease sensitive to these agents, will serve as the model tumour type to identify predictive response biomarkers suitable for widespread application across diverse tumour types. PREDICT’s biomarker discovery approach is based on the integration of genomics data from pre-operative RCC therapeutic clinical trials with novel personalised functional genomic screen datasets. We will systematically collect tumour tissue from monotherapy pre-operative window RCC clinical trials of 240 patients treated with everolimus or sunitinib and determine expression profiles, copy number aberrations, and genome-wide exon sequences of tumours before and after drug treatment. We will perform two types of RNA interference drug- and hypoxia-resistance screens: one using reverse transfection of commercial siRNA libraries into previously established RCC cell lines, and one using a novel approach through personalised tumour cDNA derived-shRNA library transduction of ex-vivo cultured autologous tumour cell lines. Bioinformatics integration of these complementary individualised clinical and experimental datasets will enable the rapid and cost efficient identification of predictive biomarkers and simultaneously define molecular mechanisms contributing to intrinsic and acquired drug resistant disease in vivo, yielding additional targets for therapeutic intervention.

Field of science

  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

FP7-HEALTH-2010-two-stage
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

DANMARKS TEKNISKE UNIVERSITET
Address
Anker Engelundsvej 1 Bygning 101 A
2800 Kgs Lyngby
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 762 240
Administrative Contact
Marlene Beck (Ms.)

Participants (13)

CANCER RESEARCH UK LBG
United Kingdom
EU contribution
€ 1 483 296
Address
St John Street 407 Angel Building
EC1V 4AD London
Activity type
Research Organisations
Administrative Contact
Louisa Jacobs (Ms.)
GENOME RESEARCH LIMITED
United Kingdom
EU contribution
€ 517 497,60
Address
The Gibbs Building, Euston Road 215
NW1 2BE London
Activity type
Research Organisations
Administrative Contact
Angela Macharia (Ms.)
THE ROYAL MARSDEN NATIONAL HEALTH SERVICE TRUST
United Kingdom
EU contribution
€ 688 500
Address
Fulham Road 203-6
SW3 6JJ London
Activity type
Research Organisations
Administrative Contact
James Larkin (Dr.)
INSTITUT GUSTAVE ROUSSY
France
EU contribution
€ 376 440
Address
Rue Camille Desmoulins 39
94805 Villejuif
Activity type
Research Organisations
Administrative Contact
Arnauld Forest (Mr.)
SEMMELWEIS EGYETEM
Hungary
EU contribution
€ 322 633,60
Address
Ulloi Utca 26
1085 Budapest
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Balazs Gyorffy (Dr.)
NATURWISSENSCHAFTLICHES UND MEDIZINISCHES INSTITUT AN DER UNIVERSITAET TUEBINGEN
Germany
EU contribution
€ 516 702
Address
Markwiesenstrasse 55
72770 Reutlingen
Activity type
Research Organisations
Administrative Contact
Thomas Schweikert (Mr.)
EXPERIMENTELLE PHARMAKOLOGIE UND ONKOLOGIE BERLIN-BUCH GMBH
Germany
EU contribution
€ 284 250
Address
Robert-roessle-strasse 10
13125 Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jens Hoffmann (Dr.)
Horizon Discovery Limited
United Kingdom
EU contribution
€ 171 750
Address
Cambridge Research Park
CB25 9TL Cambridge
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Torrance Christopher (Dr.)
Bayer Pharma AG
Germany
EU contribution
€ 328 700
Address
Muellerstrasse 178
13353 Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Hans-Dieter Pohlenz (Dr.)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 46 055,20
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
Administrative Contact
Christophe Misse (Mr.)
ASSOCIATION POUR LA RECHERCHE DE THERAPEUTIQUES INNOVANTES EN CANCEROLOGIE
France
EU contribution
€ 330 944,80
Address
Rue Des Bruyeres 47
94370 Sucy En Brie
Activity type
Research Organisations
Administrative Contact
Reza Elaidi (Dr.)
QUEEN MARY UNIVERSITY OF LONDON
United Kingdom
EU contribution
€ 6 000
Address
327 Mile End Road
E1 4NS London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Thomas Powles (Dr.)
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Netherlands
EU contribution
€ 6 000
Address
Plesmanlaan 121
1066 CX Amsterdam
Activity type
Research Organisations
Administrative Contact
Henri G.A.M. Van Luenen (Mr.)