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GlioTarget SIGNED

Inflaming the microenvironment of glioblastoma tumors by ADAR1 inhibition: a two-hit approach for the treatment of brain cancer.

Total Cost €

0

EC-Contrib. €

0

Partnership

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 GlioTarget project word cloud

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

expression    orchestrate    functions    immunity    memories    acting    primary    patient    lethal    immuno    immune    supporting    vulnerability    interferon    date    gb    lines    pointing    models    hinder    combine    diagnosed    individuals    vital    survival    inflammation    central    care    deaminase    nucleic    disheartening    15    immunosuppressive    aberrant    glioblastomas    simultaneously    sensing    newly    patients    extreme    form    interactions    acids    standard    checkpoint    representing    microenvironment    malignancies    adar1    expressing    functionally    endogenous    rna    therapeutic    adenosine    stimulated    infiltration    experiences    emerged    molecular    tme    14    invariably    tumors    mouse    cell    gbs    disrupt    cancer    foreign    alone    genetic    isg    frequent    organ    months    perform    inhibit    understand    core    therapy    pharmacologic    dsrnas    trigger    ultimately    therapies    stores    otherwise    isgs    inhibition    fail    heterogeneity    body    innate    despite    social    clinical    immunotherapies    self    cells    leads    outcomes    median    tumor    oncology    precious    sensitivity    edits    arrest    human    nature    combination    brain    genes   

Project "GlioTarget" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE LAUSANNE 

Organization address
address: Quartier Unil-Centre Bâtiment Unicentre
city: LAUSANNE
postcode: 1015
website: www.unil.ch

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 Switzerland [CH]
 Total cost 191˙149 €
 EC max contribution 191˙149 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2019
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2021
 Duration (year-month-day) from 2021-09-01   to  2023-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE LAUSANNE CH (LAUSANNE) coordinator 191˙149.00

Map

 Project objective

The brain is our most precious organ. Not only does it orchestrate vital body functions but it also stores memories and experiences, ultimately defining the core of our human nature. Brain malignancies are particularly disheartening because they disrupt our ability to perform as individuals and hinder our social interactions. Glioblastomas (GBs) represent the most frequent and lethal form of primary brain tumors, with a median survival of 14.6 months and 15,000 newly diagnosed patients per year in Europe and the US. Current therapies invariably fail, likely due to the extreme genetic heterogeneity of GB and the presence of a highly immunosuppressive tumor microenvironment (TME). Here, I propose to exploit an innate immunity checkpoint to simultaneously target cancer cells and their supporting TME. Adenosine Deaminase Acting on RNA 1 (ADAR1) is a central component of the RNA sensing pathway. It edits endogenous self dsRNAs, which would otherwise be recognized as foreign and trigger an aberrant innate immune response. Sensing of foreign nucleic acids results in interferon production which leads to cell-growth arrest, inflammation and immune cell infiltration through the expression of interferon-stimulated genes (ISGs). ADAR1 has recently emerged as a promising immuno-oncology target, with evidence pointing towards ADAR1 loss representing a novel vulnerability of ISG-expressing cancer cells. Despite expressing ISGs, GB tumors have not been evaluated for sensitivity to ADAR1 inhibition to date. I will therefore combine genetic and pharmacologic approaches to inhibit ADAR1 in patient-derived cancer cell lines and pre-clinical mouse models of GB. My aims are: i) to understand the molecular outcomes of ADAR1 inhibition in GB cancer cells; ii) to functionally characterize the TME of GBs upon ADAR1 inhibition; iii) to evaluate the therapeutic potential of ADAR1 inhibition alone and in combination with standard of care therapy and TME-targeted immunotherapies.

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

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