PT - JOURNAL ARTICLE AU - Jun Lu AU - Hua Zhong AU - Tianqing Chu AU - Xueyan Zhang AU - Rong Li AU - Jiayuan Sun AU - Runbo Zhong AU - Yuqin Yang AU - Mohammad Shah Alam AU - Yuqing Lou AU - Jianlin Xu AU - Yanwei Zhang AU - Jun Wu AU - Xiaowei Li AU - Xiaodong Zhao AU - Kai Li AU - Liming Lu AU - Baohui Han TI - Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for non-small cell lung cancer therapy AID - 10.1183/13993003.01562-2018 DP - 2018 Jan 01 TA - European Respiratory Journal PG - 1801562 4099 - http://erj.ersjournals.com/content/early/2018/12/05/13993003.01562-2018.short 4100 - http://erj.ersjournals.com/content/early/2018/12/05/13993003.01562-2018.full AB - Background Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced non-small cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear.Methods A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the anti-tumour molecular mechanisms of anlotinib. Changes in serum CCL2 levels were analysed to examine the correlation of the anlotinib response between responders and non-responders.Results Anlotinib therapy was beneficial for prolonging OS in NSCLC patients harbouring positive driver gene mutations, especially patients harbouring the EGFRT790M mutation. Moreover, anlotinib inhibited angiogenesis in an NCI-H1975-derived xenograft model via inhibiting CCL2. Finally, anlotinib-induced serum CCL2 level decreases were associated with the benefits of PFS and OS in refractory advanced NSCLC patients.Conclusions Our study reports a novel anti-angiogenesis mechanism of anlotinib via inhibiting CCL2 in an NCI-H1975-derived xenograft model and suggests that changes in serum CCL2 levels may be used to monitor and predict clinical outcomes in anlotinib-administered refractory advanced NSCLC patients using third-line therapy or beyond.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Han has nothing to disclose.Conflict of interest: Dr. H. Zhong has nothing to disclose.Conflict of interest: Dr. Xu has nothing to disclose.Conflict of interest: Dr. Sun has nothing to disclose.Conflict of interest: Dr. Lu has nothing to disclose.Conflict of interest: Dr. Wu has nothing to disclose.Conflict of interest: Dr. Li has nothing to disclose.Conflict of interest: Dr. L. Lu has nothing to disclose.Conflict of interest: Dr. Alam has nothing to disclose.Conflict of interest: Dr. R. Li has nothing to disclose.Conflict of interest: Dr. R. Zhong has nothing to disclose.Conflict of interest: Dr. Chu has nothing to disclose.Conflict of interest: Dr. Zhao has nothing to disclose.Conflict of interest: Dr. X. Li has nothing to disclose.Conflict of interest: Dr. X. Zhang has nothing to disclose.Conflict of interest: Dr. Y. Zhang has nothing to disclose.Conflict of interest: Dr. Yang has nothing to disclose.Conflict of interest: Dr. Lou has nothing to disclose.