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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00471938" target="_blank" >RIV/68081707:_____/16:00471938 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/16:00092582

Result on the web

<a href="http://dx.doi.org/10.1038/ncomms13701" target="_blank" >http://dx.doi.org/10.1038/ncomms13701</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ncomms13701" target="_blank" >10.1038/ncomms13701</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

BO - Biophysics

OECD FORD branch

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Project

<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

DEC2016

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

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UT code for WoS article

000389180300001

EID of the result in the Scopus database

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