Multi-kinase targets of sorafenib (None)

Sorafenib is a potent multi-kinase inhibitor that targets a broad spectrum of intracellular and cell surface kinases involved in tumor growth and angiogenesis [1, 2]. Its primary targets include the RAF serine/threonine kinases (RAF-1, wild-type B-RAF, and mutant B-RAF V600E) and several receptor tyrosine kinases, such as vascular endothelial growth factor receptors (VEGFR-1, -2, -3), platelet-derived growth factor receptor-beta (PDGFR-beta), KIT, FLT-3, and RET [1, 3, 5]. By inhibiting these pathways, sorafenib exerts a dual effect: it directly suppresses tumor cell proliferation through the RAF/MEK/ERK signaling cascade and indirectly inhibits tumor growth by disrupting the tumor microvasculature and angiogenesis [1, 6, 15]. Clinically, sorafenib is a standard-of-care treatment for advanced hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and differentiated thyroid carcinoma [2, 8, 10]. It is also investigated for use in other malignancies like acute myeloid leukemia (AML) due to its activity against FLT-3 [2, 10]. Common therapeutic challenges include managing systemic toxicities such as hand-foot skin reaction and hypertension, which are often dose-limiting [9, 11, 13].

Other names

Sorafenib targetsNexavar targetsVEGFR/PDGFR/RAF kinasesRAF/VEGFR/PDGFR kinases

Inhibition of intracellular RAF kinases (RAF-1, B-RAF) and cell surface receptor tyrosine kinases (VEGFR, PDGFR, KIT, FLT-3, RET), leading to decreased tumor cell proliferation and reduced tumor angiogenesis [1, 2, 5].