Multi-kinase targets (RAF, VEGFR, PDGFR, KIT, FLT3, and IGF-1R)

This target entry refers to a collection of signaling proteins inhibited by the drug sorafenib and the monoclonal antibody BIIB022. Sorafenib is a multi-kinase inhibitor that targets several receptor tyrosine kinases (RTKs) and serine/threonine kinases, including RAF-1, B-RAF, Vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), Platelet-derived growth factor receptor beta (PDGFR-beta), KIT, and FLT3 [1, 2, 6]. These proteins are critical components of the MAPK/ERK pathway and are essential for tumor angiogenesis and cell survival [1, 6]. BIIB022 is an investigational humanized monoclonal antibody that specifically targets the Insulin-like growth factor 1 receptor (IGF-1R) [3, 5]. IGF-1R is a transmembrane RTK that promotes cell growth and inhibits apoptosis, often being overexpressed in various solid tumors [5]. The combination of these targets represents a broad therapeutic strategy to disrupt multiple pathways necessary for oncogenesis and tumor maintenance [1, 4]. Clinically, drugs hitting these targets are used or studied for the treatment of hepatocellular carcinoma, renal cell carcinoma, and other advanced malignancies [2, 6]. Inhibition of these pathways can lead to significant therapeutic benefits but is also associated with specific toxicities such as hand-foot skin reaction and hypertension [6].

Other names

Sorafenib targetsBIIB022 targetInsulin-like growth factor 1 receptorVascular endothelial growth factor receptorRAF proto-oncogene serine/threonine-protein kinasePlatelet-derived growth factor receptorKIT proto-oncogene receptor tyrosine kinaseFms-like tyrosine kinase 3

Inhibition of multiple intracellular and receptor tyrosine kinases to block tumor cell signaling, proliferation, and angiogenesis.