Anlotinib can overcome acquired resistance to EGFR-TKIs via FGFR1 signaling in non-small cell lung cancer

Background: As a novel multitarget receptor tyrosine kinase inhibitor, anlotinib has been demonstrated to be effective in inhibition of tumor angiogenesis and growth. Interestingly, a subset of advanced non-small cell lung cancer (NSCLC) patients who are refractory to EGFR-TKIs are sensitive to anlotinib treatment, the underlying molecular mechanism remained unclear. Herein, we mainly focus on elucidating the regulatory mechanism treated with anlotinib in overcoming acquired resistance to EGFR-TKIs in NSCLC and thus may develop novel therapeutic strategies for anlotinib aiming at improving the prognosis of patients resistant to TKIs. Methods: High throughput sequencing analysis, western blot analysis, real-time quantitative reverse transcriptase PCR, RNA interference, CCK-8 and flow cytometry were performed on human NSCLC EGFR-resistant cell lines. Results: Based on high-throughput sequencing analysis, FGFR1 was highly expressed in gefitinib-resistant cell line when compared to HCC827. In line with the data, anlotinib application obviously inhibitied cell viability, proliferation and promoted apoptosis in HCC827GR cell line. Knockdown of FGFR1 can reverse gefitinib resistance. Research into possible mechanisms indicated that anlotinib treatment down-regulated the phosphorylation levels of Erk and Akt. Conclusions: Anlotinib can overcome acquired resistance to EGFR-TKIs via inhibiting FGFR1 signaling pathway, which provide a mechanism evidence for the treatment of NSCLC patients. Legal entity responsible for the study: The First Affiliated Hospital of Soochow University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.