Resumen
Bevacizumab mediated anti-angiogenesis provides a new chance of survival for patients with a tumor. However, most patients have acquired bevacizumab resistance after continuous treatment, and there is no available clinical therapy to overcome drug resistance. In this study, we analyzed unique expression patterns of genes from bevacizumab-sensitive or acquired bevacizumab-resistant cancer cells using RNA-seq analysis to identify the potential molecules and mechanism of bevacizumab resistance. We found that endothelial-specific molecule 1 expression elevated bevacizumab-resistant tumor cells, and endothelial-specific molecule 1 further regulates MMP9, VEGF, and DLL4 to promote metastasis and angiogenesis in vitro and in vivo. The anti-ESM1 monoclonal antibody developed by us significantly strengthened the efficacy of bevacizumab in vivo. This research has an important theoretical and clinical application value for elucidating the resistance mechanism and overcoming the bevacizumab resistance.