Multi-kinase receptor tyrosine kinase (VEGFR, PDGFR, FGFR, and c-Kit) (VEGFR/PDGFR/FGFR/c-Kit)

This target profile represents a cluster of Receptor Tyrosine Kinases (RTKs) including Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), Fibroblast Growth Factor Receptor (FGFR), and the Mast/stem cell growth factor receptor (c-Kit) (UniProt, 2024). These receptors are critical mediators of physiological and pathological angiogenesis, lymphangiogenesis, and tumor cell proliferation (Nature Reviews Drug Discovery, 2017). VEGFR primarily drives the formation of new blood vessels by stimulating endothelial cell migration and tube formation, while PDGFR and FGFR contribute to pericyte recruitment and provide escape mechanisms for tumors resistant to anti-VEGF therapy (PubMed, 2018). The c-Kit receptor is essential for the development of hematopoietic stem cells and is frequently mutated in specific malignancies like gastrointestinal stromal tumors (GIST) (StatPearls, 2023). In oncology, multi-kinase inhibitors (MKIs) are designed to simultaneously block these pathways to overcome redundant signaling and suppress both tumor growth and its supporting blood supply. Drugs such as sunitinib, pazopanib, and lenvatinib target this specific combination to treat various solid tumors, including renal cell and hepatocellular carcinomas. However, the broad inhibition of these receptors often leads to systemic side effects, most notably hypertension and dermatological toxicities like hand-foot skin reaction.

Other names

Angiogenesis-related receptor tyrosine kinasesMulti-targeted receptor tyrosine kinasesVEGFR-PDGFR-FGFR-KIT complexMulti-targeted kinase inhibitor (TKI) targets

These drugs act as competitive inhibitors of the adenosine triphosphate (ATP) binding site within the intracellular tyrosine kinase domain of the receptors (StatPearls, 2023). By blocking ATP binding, they prevent the autophosphorylation of the receptor and the subsequent activation of downstream signaling cascades such as the MAPK/ERK, PI3K/Akt, and STAT pathways, which are essential for cell survival and proliferation (PubMed, 2017).