Počet záznamů: 1  

MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated

  1. 1.
    0471938 - BFÚ 2017 RIV GB eng J - Článek v odborném periodiku
    Smida, M. - de la Cruz, F.F. - Kerzendorfer, C. - Uras, I.Z. - Mair, B. - Mazouzi, A. - Suchánková, Tereza - Konopka, T. - Katz, A.M. - Paz, K. - Nagy-Bojarszky, K. - Muellner, M.K. - Bago-Horvath, Z. - Haura, E.B. - Loizou, J.I. - Nijman, S.M.B.
    MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated.
    Nature Communications. Roč. 7, DEC2016 (2016), č. článku 13701. E-ISSN 2041-1723
    Institucionální podpora: RVO:68081707
    Klíčová slova: breast-cancer * insulin-resistance * missense mutations
    Kód oboru RIV: BO - Biofyzika
    Impakt faktor: 12.124, rok: 2016

    Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo. Mechanistically, ATM mediates crosstalk between the prosurvival MEK/ERK and AKT/mTOR pathways. ATM loss also enhances the sensitivity of KRAS- or BRAF-mutant lung cancer cells to MEK inhibition. Thus, ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours.
    Trvalý link: http://hdl.handle.net/11104/0269300

     
     
Počet záznamů: 1  

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