| ŠMÍDA, Michal, Ferran Fece DE LA CRUZ, Claudia KERZENDORFER, Iris Z. URAS, Barbara MAIR, Abdelghani MAZOUZI, Tereza SUCHANKOVA, Tomasz KONOPKA, Amanda M. KATZ, Keren PAZ, Katalin NAGY-BOJARSZKY, Markus K. MUELLNER, Zsuzsanna BAGO-HORVATH, Eric B. HAURA, Joanna I. LOIZOU a Sebastian M. B. NIJMAN. MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated. Nature Communications. London: Nature Publishing Group, 2016, roč. 7, December, s. nestránkováno, 13 s. ISSN 2041-1723. Dostupné z: https://dx.doi.org/10.1038/ncomms13701. |
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@article{1366225,
author = {Šmída, Michal and de la Cruz, Ferran Fece and Kerzendorfer, Claudia and Uras, Iris Z. and Mair, Barbara and Mazouzi, Abdelghani and Suchankova, Tereza and Konopka, Tomasz and Katz, Amanda M. and Paz, Keren and NagyandBojarszky, Katalin and Muellner, Markus K. and BagoandHorvath, Zsuzsanna and Haura, Eric B. and Loizou, Joanna I. and Nijman, Sebastian M. B.},
article_location = {London},
article_number = {December},
doi = {http://dx.doi.org/10.1038/ncomms13701},
keywords = {BREAST-CANCER; INSULIN-RESISTANCE; MISSENSE MUTATIONS; DNA-DAMAGE; ATM; AUTOPHAGY; VARIANTS; PATHWAYS; MTORC1; CELLS},
language = {eng},
issn = {2041-1723},
journal = {Nature Communications},
title = {MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated},
url = {http://www.nature.com/articles/ncomms13701},
volume = {7},
year = {2016}
}
TY - JOUR
ID - 1366225
AU - Šmída, Michal - de la Cruz, Ferran Fece - Kerzendorfer, Claudia - Uras, Iris Z. - Mair, Barbara - Mazouzi, Abdelghani - Suchankova, Tereza - Konopka, Tomasz - Katz, Amanda M. - Paz, Keren - Nagy-Bojarszky, Katalin - Muellner, Markus K. - Bago-Horvath, Zsuzsanna - Haura, Eric B. - Loizou, Joanna I. - Nijman, Sebastian M. B.
PY - 2016
TI - MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated
JF - Nature Communications
VL - 7
IS - December
SP - nestránkováno
EP - nestránkováno
PB - Nature Publishing Group
SN - 20411723
KW - BREAST-CANCER
KW - INSULIN-RESISTANCE
KW - MISSENSE MUTATIONS
KW - DNA-DAMAGE
KW - ATM
KW - AUTOPHAGY
KW - VARIANTS
KW - PATHWAYS
KW - MTORC1
KW - CELLS
UR - http://www.nature.com/articles/ncomms13701
L2 - http://www.nature.com/articles/ncomms13701
N2 - 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.
ER -
ŠMÍDA, Michal, Ferran Fece DE LA CRUZ, Claudia KERZENDORFER, Iris Z. URAS, Barbara MAIR, Abdelghani MAZOUZI, Tereza SUCHANKOVA, Tomasz KONOPKA, Amanda M. KATZ, Keren PAZ, Katalin NAGY-BOJARSZKY, Markus K. MUELLNER, Zsuzsanna BAGO-HORVATH, Eric B. HAURA, Joanna I. LOIZOU a Sebastian M. B. NIJMAN. MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated. \textit{Nature Communications}. London: Nature Publishing Group, 2016, roč.~7, December, s.~nestránkováno, 13 s. ISSN~2041-1723. Dostupné z: https://dx.doi.org/10.1038/ncomms13701.
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