Journal
CANCER LETTERS
Volume 322, Issue 2, Pages 213-222Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.03.015
Keywords
NSCLC; Sorafenib; Paclitaxel; Sequential combination; Xenograft mice
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Funding
- Ministry of Education & Human Resources Development in Korea
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Studies on non-small cell lung cancer (NSCLC) patients with KRAS or BRAF mutations are urgently needed to improve clinical outcomes. We evaluated the cytotoxicities of paclitaxel and sorafenib alone and in combination in NSCLC cell lines with KRAS or BRAF mutations and investigated the mechanism of the interaction between the drugs. We found synergistic antitumor efficacy with paclitaxel followed by sorafenib in in vitro and in vivo models of NSCLC. And, we determined that downregulation of the phosphorylated ERK and Rb, and Mcl-1 plays a critical role in the synergistic activity of the drugs. Further clinical trials are needed to verify the antitumor efficacy of this combination. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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