LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

Mahoney, C L, Choudhury, B, Davies, H, Edkins, S, Greenman, C, Haaften, G Van, Mironenko, T, Santarius, T, Stevens, C, Stratton, M R and Futreal, P A (2009) LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition. British Journal of Cancer, 100 (2). pp. 370-375. ISSN 1532-1827

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Computing Sciences Faculty of Medicine and Health Sciences > School of Rehabilitation Sciences (former - to 2014)
UEA Research Groups:	Faculty of Science > Research Groups > Computational Biology
Depositing User:	Christopher Greenman
Date Deposited:	22 Jun 2011 11:06
Last Modified:	22 Apr 2023 00:37
URI:	https://ueaeprints.uea.ac.uk/id/eprint/30595
DOI:	10.1038/sj.bjc.6604886

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