Rapidly Accelerated Fibrosarcoma kinase (RAF) (RAF)

RAF kinases, comprising the isoforms A-RAF, B-RAF, and C-RAF (RAF-1), are essential serine/threonine kinases that function as key components of the mitogen-activated protein kinase (MAPK) signaling pathway [6, 13, 14]. This pathway is a central regulator of fundamental cellular processes, including proliferation, differentiation, and survival, by transmitting signals from cell surface receptors to the nucleus [6, 16]. Dysregulation of RAF signaling, often through activating mutations such as the BRAF V600E substitution or upstream RAS mutations, is a primary driver in various human malignancies, including melanoma, thyroid cancer, and hepatocellular carcinoma [6, 16, 17]. Sorafenib is a first-generation, orally active multi-kinase inhibitor that targets the ATP-binding site of RAF kinases, particularly C-RAF and B-RAF, to block their catalytic activity [1, 2, 15]. In addition to its effects on the RAF/MEK/ERK cascade, sorafenib inhibits several receptor tyrosine kinases involved in tumor angiogenesis, such as VEGFR and PDGFR [1, 10, 15]. By disrupting these dual pathways, sorafenib suppresses tumor cell growth and induces apoptosis while simultaneously inhibiting the formation of tumor-associated blood vessels [5, 10]. It is clinically approved for the treatment of advanced hepatocellular carcinoma, renal cell carcinoma, and radioactive iodine-refractory differentiated thyroid cancer [4, 10, 15].

Other names

RAF-1C-RAFB-RAFA-RAFSerine/threonine-protein kinase Rafv-Raf murine sarcoma viral oncogene homolog

Inhibition of serine/threonine kinase activity, blocking the MAPK/ERK signaling pathway