Vascular endothelial growth factor receptor 1, 2, and 3 and Platelet-derived growth factor receptor beta (VEGFR1/2/3 and PDGFRβ)

Vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3) and platelet-derived growth factor receptor beta (PDGFRβ) are a group of receptor tyrosine kinases that play fundamental roles in the formation and maintenance of the circulatory and lymphatic systems (Wilhelm et al., 2008; Oncology Central, 2015). VEGFR2 is the primary mediator of angiogenesis, promoting endothelial cell proliferation and migration, while VEGFR3 is essential for lymphangiogenesis (PMC, 2016). PDGFRβ is critical for the recruitment of pericytes and smooth muscle cells, which stabilize newly formed blood vessels (Wilhelm et al., 2008). In many cancers, these receptors are overexpressed or activated by ligands secreted by tumor cells, facilitating the development of a tumor-associated vasculature that supports growth and metastasis (Wilhelm et al., 2008; PMC, 2016). Sorafenib is a first-in-class oral multikinase inhibitor that targets these receptors along with Raf serine/threonine kinases (Oncology Central, 2015). By inhibiting these pathways, sorafenib exerts a dual effect: it directly suppresses tumor cell proliferation and disrupts the tumor's blood supply by inhibiting angiogenesis (Wilhelm et al., 2008). It is clinically approved for the treatment of advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and radioactive iodine-refractory differentiated thyroid cancer (Oncology Central, 2015; PMC, 2015).

Other names

FLT1 (Fms-like tyrosine kinase 1)KDR (Kinase insert domain receptor)FLT4 (Fms-like tyrosine kinase 4)PDGFRB (Platelet-derived growth factor receptor beta)CD140bFlk-1VEGFR-1VEGFR-2VEGFR-3PDGFR-beta

Multi-kinase inhibition through competitive binding to the ATP-binding site of the intracellular tyrosine kinase domain, thereby blocking downstream signaling pathways such as RAS/RAF/MEK/ERK and PI3K/AKT (Wilhelm et al., 2008; ResearchGate, 2021).