Rapidly Accelerated Fibrosarcoma (RAF), Vascular Endothelial Growth Factor Receptor (VEGFR), and Platelet-Derived Growth Factor Receptor (PDGFR) family kinases (RAF/VEGFR/PDGFR)

The RAF/VEGFR/PDGFR family kinases represent a critical multi-target signaling axis involved in both tumor cell proliferation and the maintenance of the tumor microenvironment. RAF kinases (A-RAF, B-RAF, and C-RAF) are intracellular serine/threonine kinases that function within the RAS/RAF/MEK/ERK pathway to drive cell growth, differentiation, and survival [1, 13]. In contrast, VEGFR (Vascular Endothelial Growth Factor Receptor) and PDGFR (Platelet-Derived Growth Factor Receptor) are receptor tyrosine kinases that primarily regulate angiogenesis and vascular stability by acting on endothelial cells and pericytes, respectively [12, 25]. Dysregulation of these pathways is a hallmark of various malignancies, including hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer, where they promote uncontrolled growth and neovascularization [4, 5]. Therapeutic targeting of this family is achieved through multi-kinase inhibitors like sorafenib and regorafenib, which provide a dual mechanism of action by directly inhibiting tumor cells and starving them of blood supply [2, 6]. While effective, these inhibitors are associated with distinct class-effect toxicities such as hypertension, hand-foot skin reactions, and cardiovascular complications [14, 16].

Other names

RAF/VEGFR/PDGFR kinasesMulti-kinase targetRAF/VEGFR/PDGFR signaling axisSorafenib targetsRegorafenib targets

Inhibition of kinase activity through ATP-competitive or allosteric binding, leading to the blockade of the RAS/RAF/MEK/ERK signaling pathway and the inhibition of VEGF/PDGF-mediated angiogenesis and vascular stabilization.