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KMID : 0379520230390010061
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한국독성학회지
2023 Volume.39 No. 1 p.61 ~ p.69
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CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer
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Kim Soo-Jin
Lee Kyung-Hyeon
Park Jae-Woo
Park Mi-So
Kim U.-Ji
Kim Se-Mi
Ryu Keun-Ho
Kang Keon-Wook
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Abstract
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Lung cancer is the leading cause of cancer death. Although docetaxel has been used as a second- or third-line treatment for non-small cell lung cancer (NSCLC), the objective response rate is less than 10%. Hence, there is a need to improve the clinical efficacy of docetaxel monotherapy; combination therapy should be considered. Here, we show that CKD-516, a vascular disruption agent, can be combined with docetaxel to treat epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant NSCLC. CKD-516 was orally bioavailable; neither CKD-516 nor docetaxel affected the mean plasma concentration?time profile or pharmacokinetic parameters of the other drug. CKD-516 and docetaxel synergistically inhibited the growth of H1975 (with an L858R/T790M double mutation of EGFR) and A549 (with a KRAS mutation) lung cancer cell lines. In addition, docetaxel plus CKD-516 delayed tumor growth in?and extended the lifespan of?tumor-bearing mice. Thus, combination CKD-516 and docetaxel therapy could be used to treat EGFR-TKI-resistant NSCLC.
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KEYWORD
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CKD-516, Docetaxel, TKI-resistant NSCLC, Vascular disrupting agent
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