Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

The Rearranged during transfection (RET) fusion gene has recently been identified as an oncogenic mutation in non-small cell lung cancer (NSCLC). This study aims to investigate the biological functions of the RET fusion gene in tumorigenesis and metastasis using preclinical models driven by RET gene fusion. Additionally, we examine the anti-tumor effects of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src, and RET, in RET-rearranged lung adenocarcinoma, along with the underlying mechanisms. Our findings suggest that the KIF5B-RET fusion gene enhances cell invasion and migration, likely through the Src signaling pathway. Apatinib demonstrated anti-cancer activity not only by inducing cytotoxicity but also by inhibiting migration and invasion by suppressing the RET/Src signaling pathway.TPX-0046 These results support the potential of Apatinib as a therapeutic option for KIF5B-RET driven tumors.