Abstract 5054: The study of synergy mechanism between surufatinib and vinorelbine in the treatment of non-small cell lung cancer
Authors: Wu Xiaoran , Zheng Yanfang , Qin Lingyu , Li Ying , Yu Zhongjian , Zhu Xiongjie , Cai Rui , Niu Feiyu , Yuan Yan , Jiang Peng , Wen Shaoshi , Lv Xing , Zhou Jiancai 
Published: April 2023

Abstract
Background: The incidence and mortality rate of lung cancer ranks first among malignant tumors. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Combined use of targeted therapy can enhance the efficacy of chemotherapy drugs while reduce the related side effects in clinical practice. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, Fibroblast growth factor receptor 1 (FGFR1), and CSF-1R, which simultaneously prevents tumor angiogenesis and tumor immune evasion. Our clinical study (NCT04922658) has showed the promising effect and safety of surufatinib plus vinorelbine in NSCLC patients, but the potential mechanism is still to be revealed. Herein, tumor-bearing models and cancer cell culture platform would be established for further studying, which may shed light on the synergy mechanism between surufatinib and vinorelbine, and guide the clinical treatment ultimately.
Methods: Subcutaneous tumorigenesis in nude mice were successfully established, and then treated with related experimental drugs. The tumor size was observed and CD31 expression of tumor tissue was measured using immunohistochemical analysis. In vitro study, the A549 and PC9 cell multiplication capacities were measured by CCK8 assay and plate cloning assay. The abilities of cancer cell migration and apoptosis were detected using cell scratch assay and flow cytometry kit, respectively.
Results: Monotherapy with surufatinib or vinorelbine showed a moderate tumor suppression, whereas the combination therapy of surufatinib and vinorelbine showed the remarkable inhibition of tumor growth in vivo. Surufatinib and the combination therapy obviously decreased the expression of CD31 in tumor issue which might cause the anti-angiogenesis. Monotherapy with surufatinib or vinorelbine significantly inhibited the proliferation of lung cancer cells (A549 cells and PC9 cells) in a concentration-dependent manner, and surufatinib could memorably promote the anti-proliferation activity of vinorelbine. As a result, combination therapy of surufatinib and vinorelbine distinctly inhibited lung cancer cell proliferation when compared with monotherapy with vinorelbine. Consistently, the synergistic effects of surufatinib plus vinorelbine were also observed in cell migration and apoptosis analysis.
Conclusions: Synergistic effect of surufatinib and vinorelbine resulted in a conspicuous tumor regression, which is consistent with the clinical observation. In a depth data analysis, surufatinib enhanced the antitumor activity of vinorelbine probably by inhibiting tumor cell proliferation and migration, suppressing tumor angiogenesis and promoting tumor apoptosis in NSCLC patients.
Citation Format: Xiaoran Wu, Yanfang Zheng, Lingyu Qin, Ying Li, Zhongjian Yu, Xiongjie Zhu, Rui Cai, Feiyu Niu, Yan Yuan, Peng Jiang, Shaoshi Wen, Xing Lv, Jiancai Zhou. The study of synergy mechanism between surufatinib and vinorelbine in the treatment of non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5054.