We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer.
- Authors
Broutin, Sophie; Stewart, Adam; Thavasu, Parames; Paci, Angelo; Bidart, Jean-Michel; Banerji, Udai
- Abstract
<bold>Background: </bold>We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cell lines.<bold>Methods: </bold>In a panel of KRAS(M) and KRAS(WT) NSCLC cell lines, we determined growth inhibition (GI) following maximal reduction in p-ERK and p-S6RP caused by trametinib (MEK inhibitor) and AZD2014 (m-TOR inhibitor), respectively.<bold>Results: </bold>GI caused by maximal m-TOR inhibition was significantly greater than GI caused by maximal MEK inhibition in the cell line panel (52% vs 18%, P<10(-4)). There was no significant difference in GI caused by maximal m-TOR compared with maximal m-TOR+MEK inhibition. However, GI caused by the combination was significantly greater in the KRAS(M) cell lines (79% vs 61%, P=0.017).<bold>Conclusions: </bold>m-TOR inhibition was more critical to GI than MEK inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cells. The combination of MEK and m-TOR inhibition was most effective in KRAS(M) cells.
- Subjects
CELL lines; CELLULAR signal transduction; LUNG cancer; LUNG tumors; ONCOGENES; RESEARCH funding; TRANSFERASES
- Publication
British Journal of Cancer, 2016, Vol 115, Issue 5, p549
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2016.220