Multiple pro-angiogenic receptor tyrosine kinases (Multi-RTKs)

Multiple pro-angiogenic receptor tyrosine kinases (RTKs) are a group of cell-surface proteins that mediate the signaling pathways responsible for the growth of new blood vessels. This functional group primarily includes the Vascular Endothelial Growth Factor Receptor (VEGFR) family, the Platelet-Derived Growth Factor Receptor (PDGFR) family, and the Fibroblast Growth Factor Receptor (FGFR) family (Ferrara, N., Nature Medicine, 2003). In a physiological state, these receptors regulate essential processes such as embryonic development, wound healing, and the female reproductive cycle. However, in the context of oncology, tumors often upregulate these pathways to stimulate pathological angiogenesis, ensuring the delivery of oxygen and nutrients required for tumor expansion and metastasis (Turner, N. & Grose, R., Nature Reviews Cancer, 2010). Multi-kinase inhibitors (MKIs) are designed to target several of these receptors simultaneously to provide more robust inhibition of the angiogenic process and to circumvent potential resistance mechanisms. While these therapies have significantly improved outcomes in various cancers, their broad-spectrum activity is frequently associated with systemic adverse effects, such as hypertension and dermatological toxicities, due to the inhibition of these kinases in non-malignant tissues (Chen, H. X. & Cleck, J. N., Journal of Clinical Oncology, 2009).

Other names

Multi-targeted receptor tyrosine kinasesAngiogenic RTKsVEGFR/PDGFR/FGFR familyPro-angiogenic RTKsMulti-kinase targets

Competitive inhibition of the ATP-binding site within the intracellular catalytic domain of multiple receptor tyrosine kinases, preventing autophosphorylation and downstream signaling (Wilhelm, S. M., et al., Nature Reviews Drug Discovery, 2006).