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onCOMBINE SIGNED

Towards evidence-based combinations of approved and novel cancer drugs

Total Cost €

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EC-Contrib. €

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Partnership

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 onCOMBINE project word cloud

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

inducing    poly    pkis    cancer    animal    generalizing    signalling    synergies    mabs    oncogene    25    receptors    intercepts    compensatory    examined    recognising    lymphoid    phosphoproteomics    toxicities    cytotoxicity    primary    protein    rarely    driver    oncology    fatalities    approved    antibodies    mechanisms    cells    awaited    background    molecular    gt    loops    mutant    inhibit    interactions    inhibitors    lung    employs    immune    rna    adaptations    once    mapping    unlike    myeloid    transcriptomics    tt    pharmacology    senescence    met    effectors    combinations    interference    offers    underlying    optimising    conceptualize    monotherapies    apoptosis    significance    deeper    axl    addictions    monoclonal    limited    homo    drugs    immunological    cocktails    epitopes    kinase    action    drug    mutations    granularity    hypothesis    guide    persistently    harness    disease    maps    receptor    bases    interface    resistance    hetero    egfr    conferring    her2    models    interceptors    chemotherapy    route    establishing    tumours    therapy    evoked    employ   

Project "onCOMBINE" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 2˙488˙306 €
 EC max contribution 2˙488˙306 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 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    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 2˙488˙306.00

Map

 Project objective

Background: Molecular targeted therapy (TT; e.g., monoclonal antibodies, mAbs, and protein kinase inhibitors, PKIs) intercepts oncogene and other addictions of tumours. However, unlike chemotherapy, which employs cocktails of drugs, only rarely does TT harness poly-pharmacology. Because lung cancer is the major cause of oncology related fatalities and many driver mutations are known, this disease offers opportunities for establishing and generalizing novel TT combinations and their interface with the immune system. Working hypothesis: High granularity maps of compensatory loops evoked by TT, along with deeper understanding of mechanisms underlying drug action, resistance and interactions with lymphoid/myeloid cells, will conceptualize drug combinations able to persistently inhibit tumours, while inducing only limited toxicities. Goal and specific aims: Addressing resistance to TT, potential synergies and the immune system, we will employ lung cancer models driven by mutant EGFR, HER2, MET or AXL. Phosphoproteomics, transcriptomics and RNA interference, will enable mapping adaptations evoked by specific drugs. Once identified, we will test combinations of interceptors able to inhibit the primary target as well as the emerging, resistance-conferring route(s). Next, we will determine the mechanisms of action of selected interceptors (e.g., apoptosis, immunological cytotoxicity and senescence) as bases for optimising effective combinations. Homo-combinations of antibodies (i.e., antibodies recognising distinct epitopes of a receptor), hetero-combinations targeting distinct signalling and immune receptors, and combinations with PKIs will be examined in animal models. Significance: More than 30 PKIs and >25 mAbs are approved in oncology, but most are used as monotherapies. Detailed knowledge of adaptation-driven resistance, mechanisms of drug action and immune effectors, will guide the long awaited application of TT combinations in oncology, including lung cancer.

 Publications

year authors and title journal last update
List of publications.
2018 D. Romaniello, L. Mazzeo, M. Mancini, I. Marrocco, A. Noronha, M. Kreitman, S. Srivastava, S. Ghosh, M. Lindzen, T.M. Salame, A. Onn, J. Barr, Y. Yarden
A Combination of Approved Antibodies Overcomes Resistance of Lung Cancer to Osimertinib by Blocking Bypass Pathways
published pages: 5610-5621, ISSN: 1557-3265, DOI: 10.1158/1078-0432.ccr-18-0450
Clinical Cancer Research Mpvember 15, 2018 2019-06-05
2018 Maicol Mancini, Hilah Gal, Nadège Gaborit, Luigi Mazzeo, Donatella Romaniello, Tomer Meir Salame, Moshit Lindzen, Georg Mahlknecht, Yehoshua Enuka, Dominick GA Burton, Lee Roth, Ashish Noronha, Ilaria Marrocco, Dan Adreka, Raya Eilam Altstadter, Emilie Bousquet, Julian Downward, Antonio Maraver, Valery Krizhanovsky, Yosef Yarden
An oligoclonal antibody durably overcomes resistance of lung cancer to third‐generation EGFR inhibitors
published pages: 294-308, ISSN: 1757-4676, DOI: 10.15252/emmm.201708076
EMBO Molecular Medicine 10/2 2019-06-05

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

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