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INTUMORX

Elucidation of intratumoral heterogeneity in Kras-driven cancers

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 INTUMORX project word cloud

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

strikingly    tissues    lentiviral    efforts    tumor    hypothesized    experiments    responder    populations    human    variability    signals    vivo    provides    probablility    luad    molecule    molecular    survival    stem    advantageous    therapy    molecules    ablation    krasg12d    indicate    kp    signal    modified    crispr    elucidate    model    cell    genetically    mice    cellular    phenotypes    hierarchical    tracing    forming    suppressed    prolonged    leads    tumors    delta    therapeutic    ed    intratumoral    inhibitors    tissue    selective    vectors    microenvironments    regeneration    collectively    small    population    combination    considerable    signaling    mouse    tp53    maintenance    reporter    autochthonous    vitro    mechanisms    lung    niche    cells    components    exhibited    silencing    reconstitution    resistant    multiclonality    cellullar    subpopulation    resistance    cancers    adenocarcinomas    demonstrated    lineage    had    heterogeneity    treatment    engineered    cancer    epithelial    propagation    stasis    normal    context    wnt   

Project "INTUMORX" data sheet

The following table provides information about the project.

Coordinator
HELSINGIN YLIOPISTO 

Organization address
address: YLIOPISTONKATU 3
city: HELSINGIN YLIOPISTO
postcode: 14
website: www.helsinki.fi

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 Finland [FI]
 Total cost 1˙972˙905 €
 EC max contribution 1˙972˙905 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELSINGIN YLIOPISTO FI (HELSINGIN YLIOPISTO) coordinator 1˙972˙905.00

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 Project objective

The considerable variability within tissue microenvironments as well as the multiclonality of cancers leads to intratumoral heterogeneity. This increases the probablility of cellular states that promote resistance to therapy and eventually lead to reconstitution of the tumor by treatment-resistant cancer cells, which in some cases have properties of normal tissue stem cells. Wnt signals are important in the maintenance of stem cells in various epithelial tissues, including in lung development and regeneration. We hypothesized that Wnt signals contribute to tumor heterogeneity in genetically engineered KrasG12D; Tp53Δ/Δ (”KP”) mouse lung adenocarcinomas (LUAD). We observed that a subpopulation of LUAD cells exhibited high Wnt reporter activity and had increased tumor forming ability, which could be suppressed by silencing of Wnt signaling pathway components or by small molecule Wnt inhibitors in vitro and in vivo. KP LUAD cells show hierarchical features with two distinct populations, one with increased Wnt reporter activity and another forming a niche that provides the Wnt signal. Lineage-tracing experiments in the autochthonous KP tumors demonstrated that Wnt responder cells have increased tumor propagation ability in vivo. Strikingly, selective ablation of the Wnt responder cells resulted in tumor stasis. CRISPR-based targeting or small molecules targeting Wnt signaling reduced tumor growth and prolonged survival in the autochthonous KP mouse lung cancer model. These results indicate that maintenance of heterogeneity within tumors may be advantageous for the tumor cell population collectively. We propose to elucidate the molecular and cellullar mechanisms that control stem-like and niche cell phenotypes using a combination of novel lentiviral vectors and genetically modified mice in the context of the KP LUAD model. These efforts may lead to novel therapeutic concepts in human lung cancer.

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

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