Multi-kinase target profile (VEGFR1-3, FGFR1, PDGFRβ, RET, KIT, RAF, TIE2) (VEGFR/FGFR/PDGFR/RET/KIT/RAF/TIE2)

This target profile represents a comprehensive set of signaling proteins, primarily receptor tyrosine kinases (RTKs) and serine/threonine kinases, that collectively drive tumor progression and survival. It includes the Vascular Endothelial Growth Factor Receptors (VEGFR1, 2, and 3) and TEK receptor tyrosine kinase (TIE2), which are essential for neoangiogenesis, lymphangiogenesis, and vascular stability within the tumor (Wilhelm et al., 2011, Nature Reviews Drug Discovery). The profile also encompasses Platelet-Derived Growth Factor Receptor beta (PDGFRβ) and Fibroblast Growth Factor Receptor 1 (FGFR1), which modulate the tumor microenvironment by influencing pericyte recruitment and stromal signaling (Grothey et al., 2013, The Lancet). Furthermore, oncogenic drivers such as KIT, RET, and the RAF family (including BRAF and CRAF) are included to address direct pathways of cell proliferation and survival (FDA Label: Stivarga). Drugs targeting this specific constellation of proteins, most notably the multi-kinase inhibitor regorafenib, are utilized to treat advanced malignancies like refractory colorectal cancer and gastrointestinal stromal tumors (GIST) by providing a multi-pronged attack on the tumor's ability to grow and recruit blood vessels. This broad inhibitory profile is designed to overcome resistance mechanisms that often arise when only a single pathway is targeted.

Other names

Regorafenib target constellationAngiogenic and oncogenic kinase profileMulti-kinase inhibitor (MKI) target setVEGFR-TIE2-FGFR-PDGFR-KIT-RET-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.