Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation

Here we report that Axitinib, an inhibitor of VEGFRs currently in use as a second line treatment for advanced renal cell carcinoma, promotes senescence of human endothelial cells in vitro. Mechanistically, this requires oxidative stress-dependent activation of the Ataxia Telangiectasia Mutated (ATM) kinase. Induction of oxidative stress-related genes distinguishes the response of endothelial cells to Axitinib from that to doxorubicin RNA-seq analysis of Human Umbilical Vein Endothelial Cells (HUVEC) treated with Axitinib and Doxorubicin pulses