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BEAT SIGNED

The functional interaction of EGFR and beta-catenin signalling in colorectal cancer: Genetics, mechanisms, and therapeutic potential.

Total Cost €

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EC-Contrib. €

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Partnership

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 BEAT project word cloud

Explore the words cloud of the BEAT project. It provides you a very rough idea of what is the project "BEAT" about.

catenin    eradication    persistence    integrative    biological    neutralisation    monoclonal    data    robustly    content    cancer    elucidate    regress    escape    linger    expression    lesions    tolerant    alterations    gene    mechanisms    egf    whereby    bases    variations    patients    therapies    regulation    wnt    fuels    rational    assisted    functional    therapy    mrd    put    innovative    benefit    genetically    tolerance    capitalises    power    platform    predictive    dependency    outputs    combined    clinically    disease    multidisciplinary    clinical    predict    tumours    fates    flexibility    samples    colorectal    abrogation    anti    signalling    portends    efficient    cells    vitro    residual    sustains    signals    substantive    genomics    vivo    opposed    antibodies    analytical    investigation    relapse    suggests    receptor    premises    prognostic    egfr    fresh    spanning    addiction    experiments    pharmacological    preliminary    sensitivity    blockade    biobank    deterioration    transcription    genetic    discovery    biomarkers    proprietary    pursued    synergy    beat    reinterpretation    beta    differentially    ensures    significance    reliance    molecular    tumour    crc    drug    unprecedented    minimal   

Project "BEAT" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI TORINO 

Organization address
address: VIA GIUSEPPE VERDI 8
city: TORINO
postcode: 10124
website: www.unito.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 1˙793˙421 €
 EC max contribution 1˙793˙421 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI TORINO IT (TORINO) coordinator 1˙793˙421.00

Map

 Project objective

Monoclonal antibodies against the EGF receptor (EGFR) provide substantive benefit to colorectal cancer (CRC) patients. However, no genetic lesions that robustly predict ‘addiction’ to the EGFR pathway have been yet identified. Further, even in tumours that regress after EGFR blockade, subsets of drug-tolerant cells often linger and foster ‘minimal residual disease’ (MRD), which portends tumour relapse. Our preliminary evidence suggests that reliance on EGFR activity, as opposed to MRD persistence, could be assisted by genetically-based variations in transcription factor partnerships and activities, gene expression outputs, and biological fates controlled by the WNT/beta-catenin pathway. On such premises, BEAT (Beta-catenin and EGFR Abrogation Therapy) will elucidate the mechanisms of EGFR dependency, and escape from it, with the goal to identify biomarkers for more efficient clinical management of CRC and develop new therapies for MRD eradication. A multidisciplinary approach will be pursued spanning from integrative gene regulation analyses to functional genomics in vitro, pharmacological experiments in vivo, and clinical investigation, to address whether: (i) specific genetic alterations of the WNT pathway affect anti-EGFR sensitivity; (ii) combined neutralisation of EGFR and WNT signals fuels MRD deterioration; (iii) data from analysis of this synergy can lead to the discovery of clinically meaningful biomarkers with predictive and prognostic significance. This proposal capitalises on a unique proprietary platform for high-content studies based on a large biobank of viable CRC samples, which ensures strong analytical power and unprecedented biological flexibility. By providing fresh insight into the mechanisms whereby WNT/beta-catenin signalling differentially sustains EGFR dependency or drug tolerance, the project is expected to put forward an innovative reinterpretation of CRC molecular bases and advance the rational application of more effective therapies.

 Publications

year authors and title journal last update
List of publications.
2019 Alberto Grand, Emanuele Geda, Andrea Mignone, Andrea Bertotti, Alessandro Fiori
One tool to find them all: a case of data integration and querying in a distributed LIMS platform
published pages: , ISSN: 1758-0463, DOI: 10.1093/database/baz004
Database 2019 2019-06-06
2019 Fiona M. Behan, Francesco Iorio, Gabriele Picco, Emanuel Gonçalves, Charlotte M. Beaver, Giorgia Migliardi, Rita Santos, Yanhua Rao, Francesco Sassi, Marika Pinnelli, Rizwan Ansari, Sarah Harper, David Adam Jackson, Rebecca McRae, Rachel Pooley, Piers Wilkinson, Dieudonne van der Meer, David Dow, Carolyn Buser-Doepner, Andrea Bertotti, Livio Trusolino, Euan A. Stronach, Julio Saez-Rodriguez, Kosuke Yusa, Mathew J. Garnett
Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens
published pages: 511-516, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1103-9
Nature 568/7753 2019-06-06

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The information about "BEAT" are provided by the European Opendata Portal: CORDIS opendata.

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