Multi-kinase target profile (VEGFR1-3, TIE2, PDGFRB, FGFR1, KIT, RET, RAF1, BRAF) (MKI profile (Regorafenib-like))

This target profile comprises a comprehensive set of kinases that drive tumor progression through multiple distinct mechanisms. It includes the vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3) and TIE2, which are essential for neoangiogenesis and lymphangiogenesis (PubMed: 21571868). The inclusion of PDGFRβ and FGFR1 targets the tumor microenvironment and pericyte recruitment, which are critical for vessel stabilization and resistance to standard anti-angiogenic therapies (PubChem: CID 11167602). Furthermore, the profile targets oncogenic drivers such as KIT and RET, along with the RAF/MEK/ERK signaling pathway via RAF1 and BRAF (including the V600E mutant), which directly promote tumor cell proliferation and survival (FDA Label: Stivarga). Drugs that inhibit this specific cluster of targets, most notably regorafenib, are utilized in the treatment of refractory metastatic colorectal cancer, advanced gastrointestinal stromal tumors, and hepatocellular carcinoma (NIH: NCT01103323). By inhibiting these diverse pathways simultaneously, the therapy aims to overcome redundant signaling mechanisms that tumors use to escape single-pathway inhibition.

Other names

Regorafenib target profileAngiogenesis and oncogenic kinase clusterVEGFR-TIE2-FGFR-PDGFR-RAF axis

Simultaneous inhibition of multiple receptor tyrosine kinases (RTKs) and intracellular serine/threonine kinases to block tumor angiogenesis, oncogenesis, and the maintenance of the tumor microenvironment.