期刊
BRITISH JOURNAL OF CANCER
卷 100, 期 2, 页码 370-375出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6604886
关键词
LKB1; KRAS; NSCLC; CI-1040; MEK
类别
资金
- Wellcome Trust
- Glaxo Smith Kline
LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.
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