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TKI resistance SIGNED

Resistance mechanisms to tyrosine kinase inhibitors in solid tumors

Total Cost €

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EC-Contrib. €

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Partnership

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 TKI resistance project word cloud

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

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Project "TKI resistance" data sheet

The following table provides information about the project.

Coordinator
INSTITUT GUSTAVE ROUSSY 

Organization address
address: Rue Camille Desmoulins 39
city: VILLEJUIF
postcode: 94805
website: http://www.igr.fr

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 France [FR]
 Project website https://www.gustaveroussy.fr/fr/biomarqueurs-predictifs-nouvelles-strategies-therapeutiques-thematique
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-12-01   to  2021-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT GUSTAVE ROUSSY FR (VILLEJUIF) coordinator 1˙500˙000.00

Map

 Project objective

Over the past 10 years, the chemotherapeutic arsenal has been expanded to include molecular-targeted therapies based on the principle that cancer cells become addicted to a single driver oncogene. However, use of these new therapies is limited due to development of acquired resistance. To fully understand how resistance develops, patient-derived models are an absolute pre-requisite, but establishing them remains extremely challenging. Few groups worldwide have successfully implemented a systematic standardized approach to facilitate translational cancer research discovery. My project aims to provide rational therapeutic guidance for combinatorial or adaptive designs to overcome acquired resistance to tyrosine kinase inhibitors (TKIs) in patients with oncogene-addiction. By establishing new laboratory models of resistance directly from patient biopsies (patient derived cell lines and xenografts) I will elucidate the molecular mechanisms whereby cancer cells escape targeted treatments. I will then implement innovative approaches to overcome resistance using TKI combinatorial screens, apoptosis sensitizers and by screening for epigenetic modifiers. Additionally, I will scrutinize the emergence of resistance acquisition in vitro. Current working models involve “persistor” cellular populations able to tolerate the TKI and, in a subsequent step, to become fully resistant to the drug. This drug tolerant persistor stage most probably involves epigenetic reprogrammation. An epigenetic inhibitor screen will be performed to identify agents able to interfere with the emergence of persistors and ultimately with the acquisition of TKI resistance. These results should provide an alternative strategy to validate innovative combinatorial drug strategies to avoid emergence of resistance in patients.

 Publications

year authors and title journal last update
List of publications.
2019 Gonzalo Recondo, Laura Mezquita, Francesco Facchinetti, David Planchard, Anas Gazzah, Ludovic Bigot, Ahsan Z Rizvi, Rosa L Frias, Jean Paul Thiery, Jean-Yves Scoazec, Tony Sourisseau, Karen Howarth, Olivier Deas, Dariia Samofalova, Justine Galissant, Pauline Tesson, Floriane Braye, Charles Naltet, Pernelle Lavaud, Linda Mahjoubi, Aurélie Abou Lovergne, Gilles Vassal, Rastilav Bahleda, Antoine Hol
Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer
published pages: clincanres.1104., ISSN: 1078-0432, DOI: 10.1158/1078-0432.ccr-19-1104
Clinical Cancer Research 2019-10-10
2019 Francesco Facchinetti, Antoine Hollebecque, Rastilav Bahleda, Yohann Loriot, Ken A Olaussen, Christophe Massard, Luc Friboulet
Facts and new hopes on selective FGFR inhibitors in solid tumors
published pages: clincanres.2035., ISSN: 1078-0432, DOI: 10.1158/1078-0432.ccr-19-2035
Clinical Cancer Research 2019-10-10
2018 Gonzalo Recondo, Francesco Facchinetti, Ken A. Olaussen, Benjamin Besse, Luc Friboulet
Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?
published pages: , ISSN: 1759-4774, DOI: 10.1038/s41571-018-0081-4
Nature Reviews Clinical Oncology 2019-09-09

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