RAF kinases and VEGFRs (RAF/VEGFRs)

RAF kinases are a family of intracellular serine/threonine kinases that act downstream of Ras in the MAPK signaling pathway, regulating cell growth, survival, apoptosis, and differentiation. Dysregulation, particularly of BRAF, is associated with oncogenic transformation and aggressive tumor phenotypes. VEGFRs are cell-surface receptor tyrosine kinases for VEGFs that are essential for regulating vascular development and pathological angiogenesis. VEGFR-2 (KDR) is the primary mediator of angiogenic signaling and is involved in tumor vascularization and metastasis. Both target families are central to cancer pathobiology and are often co-targeted by multi-kinase inhibitors for therapeutic benefit. If canonical molecular targets are required, it is preferable to split 'RAF kinases' into their main representatives (ARAF, BRAF, RAF1) and 'VEGFRs' into VEGFR-1 (Flt-1), VEGFR-2 (KDR), and VEGFR-3 (Flt-4). The joint entry is not a true canonical target but appropriately describes the pharmacological intent of drugs like sorafenib that simultaneously inhibit both signaling families.

Other names

c-RAFRAF1BRAFARAFv-RafRapidly Accelerated Fibrosarcoma kinaseVEGF receptor 1 (Flt-1)VEGF receptor 2 (KDR, Flk-1)VEGF receptor 3 (Flt-4)kinase insert domain-containing receptor (KDR)fetal liver kinase 1 (Flk-1)

Inhibition of RAF kinases blocks the MAPK/ERK signaling pathway, reducing cell proliferation and survival. Inhibition of VEGFRs prevents receptor activation upon VEGF binding, suppressing angiogenesis and neovascularization.