Vascular endothelial growth factor receptors 1-3, platelet-derived growth factor receptors alpha and beta, and fibroblast growth factor receptors 1-3 (VEGFR1-3/PDGFR-α/β/FGFR1-3)

The target profile consisting of Vascular Endothelial Growth Factor Receptors (VEGFR1-3), Platelet-Derived Growth Factor Receptors (PDGFR-α/β), and Fibroblast Growth Factor Receptors (FGFR1-3) represents a critical axis in the regulation of angiogenesis and tissue remodeling (Ferrara, 2004, Nature Reviews Cancer). VEGFRs are primarily responsible for the initiation of blood and lymphatic vessel growth, while PDGFRs and FGFRs facilitate the recruitment of mural cells and the activation of fibroblasts, ensuring structural integrity and metabolic support for new vessels (Hilberg et al., 2008, Cancer Res). In the context of malignancy, these receptors are often overexpressed or hyperactivated, promoting tumor vascularization, metastasis, and the development of a pro-tumorigenic microenvironment. Multi-targeted tyrosine kinase inhibitors (TKIs) like nintedanib and lenvatinib are designed to simultaneously block these pathways to achieve more robust inhibition of tumor growth and to overcome resistance mechanisms associated with single-pathway blockade (Matsui et al., 2011, Clin Cancer Res). This multi-pathway inhibition helps to circumvent compensatory signaling that often leads to drug resistance in oncology. Beyond oncology, these receptors play a critical role in the pathogenesis of fibrotic diseases, such as idiopathic pulmonary fibrosis, where their overactivity leads to excessive extracellular matrix deposition (Richeldi et al., 2014, NEJM). Clinical use of drugs targeting these receptors requires careful management of class-related toxicities, including hypertension and impaired wound healing, which result from the systemic inhibition of physiological angiogenesis (Chen and Cleck, 2009, Nature Reviews Clinical Oncology). Overall, this receptor group is a cornerstone of modern anti-angiogenic and anti-fibrotic therapy.

Other names

Triple angiokinase receptorsMulti-targeted receptor tyrosine kinasesAngiogenic growth factor receptorsVEGF/PDGF/FGF receptor family

Competitive inhibition of the adenosine triphosphate (ATP) binding site on the intracellular kinase domains of the receptors, preventing autophosphorylation and downstream signaling cascades (Hilberg et al., 2008, Cancer Res).