TY - JOUR
T1 - Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer
AU - Broutin, Sophie
AU - Stewart, Adam
AU - Thavasu, Parames
AU - Paci, Angelo
AU - Bidart, Jean Michel
AU - Banerji, Udai
N1 - Publisher Copyright:
© 2016 Cancer Research UK.
PY - 2016/8/23
Y1 - 2016/8/23
N2 - Background:We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR WT /ALK non-rearranged NSCLC cell lines.Methods: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.Results: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).Conclusions: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.
AB - Background:We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR WT /ALK non-rearranged NSCLC cell lines.Methods: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.Results: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).Conclusions: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.
KW - drug combinations; NSCLC; KRAS mutant; MEK inhibitor; trametinib; m-TOR inhibitor; AZD2014
UR - http://www.scopus.com/inward/record.url?scp=84979281120&partnerID=8YFLogxK
U2 - 10.1038/bjc.2016.220
DO - 10.1038/bjc.2016.220
M3 - Article
C2 - 27441499
AN - SCOPUS:84979281120
SN - 0007-0920
VL - 115
SP - 549
EP - 552
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -