Sorafenib, Salazar and Feini kinase inhibitors have dual effects of inhibiting tumor cell proliferation and tumor angiogenesis. Its mechanism of action: (1) Raf kinase, which inhibits the proliferation of tumor cells in vitro, is a serine/threonine protein kinase, a downstream effector molecule of Ras protein, and an activated Raf/MEK/ERK signaling pathway, which mediates cell proliferation, differentiation and transformation. Sorafenib can directly inhibit tumor growth by inhibiting Raf kinase, Raf- 1 specific inhibition (C-Raf), wild-type and mutant B-Raf activities. (2) Inhibition of tumor angiogenesis: By inhibiting the phosphorylation activation of receptor tyrosine kinases [including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR-β)-β, FLT-3, c-Kit and P38-α], angiogenesis and tumor progression are blocked. And sorafenib inhibit the activities of Raf- 1 and B-Raf, which are involved in controlling the apoptosis of vascular endothelial cells and may also affect angiogenesis.
Bevacizumab is a recombinant humanized monoclonal antibody against VEGF. Role of vascular endothelial growth factor-mediated angiogenesis in normal and malignant tumors of vascular system. VEGF is highly expressed in most malignant tumors, which is related to the metastasis and poor prognosis of many malignant tumors. Bevacizumab recognizes two binding sites of human vascular endothelial growth factor receptor (FLT- 1 and flk- 1), which can bind and express in various forms of VEGF. Animal experiments show that bevacizumab can stabilize or inhibit tumor growth by inhibiting VEGF-induced hemangioma.
Excerpted from China Physician Yamatonokusushi's Guide to Clinical Medication.