Počet záznamů: 1
MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated
- 1.
SYSNO ASEP 0471938 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated Tvůrce(i) Smida, M. (DE)
de la Cruz, F.F. (GB)
Kerzendorfer, C. (AT)
Uras, I.Z. (AT)
Mair, B. (AT)
Mazouzi, A. (AT)
Suchánková, Tereza (BFU-R) RID, ORCID
Konopka, T. (GB)
Katz, A.M. (US)
Paz, K. (US)
Nagy-Bojarszky, K. (AT)
Muellner, M.K. (AT)
Bago-Horvath, Z. (AT)
Haura, E.B. (AT)
Loizou, J.I. (AT)
Nijman, S.M.B. (AT)Celkový počet autorů 16 Číslo článku 13701 Zdroj.dok. Nature Communications. - : Nature Publishing Group - ISSN 2041-1723
Roč. 7, DEC2016 (2016)Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova breast-cancer ; insulin-resistance ; missense mutations Vědní obor RIV BO - Biofyzika Institucionální podpora BFU-R - RVO:68081707 UT WOS 000389180300001 DOI https://doi.org/10.1038/ncomms13701 Anotace 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. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2017
Počet záznamů: 1