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This group contains multiple closely related receptor tyrosine kinases—including vascular endothelial growth factor receptors (VEGFR-1, -2, -3), fibroblast growth factor receptors (FGFR-1, -2, -3, -4), platelet-derived growth factor receptors (PDGFR-α and -β), mast/stem cell growth factor receptor (KIT/c-Kit), and rearranged during transfection proto-oncogene (RET) receptor. They are critical mediators of growth factor signaling in angiogenesis, cell proliferation, differentiation, and survival, and have well-established roles in cancer, both as oncogenic drivers and as mediators of the tumor microenvironment. Multi-target tyrosine kinase inhibitors frequently inhibit several of these RTKs to overcome redundancy and resistance, forming a cornerstone of therapy in renal cell carcinoma, thyroid cancer, gastrointestinal stromal tumors, and other malignancies. Adverse effects often arise from the blockade of physiological signaling needed for normal vascular function.
Competitive inhibition of ATP binding at the tyrosine kinase domain (Tyrosine kinase inhibitor, TKI) Occasionally, ligand sequestration (e.g., anti-VEGF antibodies as indirect RTK inhibitors)
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