Multi-kinase receptor tyrosine kinase panel (VEGFR, FGFR, PDGFR, KIT, MET, RET, EGFR, ALK, ABL, DDR2, EphB4) (VEGFR/FGFR/PDGFR/KIT/MET/RET/EGFR/ALK/ABL/DDR2/EphB4)

This target profile represents a comprehensive collection of receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases that are pivotal in regulating cellular growth, survival, and the tumor microenvironment. The panel includes the Vascular Endothelial Growth Factor Receptor (VEGFR) family, which drives angiogenesis; the Fibroblast Growth Factor Receptor (FGFR) and Platelet-Derived Growth Factor Receptor (PDGFR) families, which regulate mesenchymal cell proliferation and development; and other critical oncogenic drivers such as MET, RET, EGFR, and ALK (UniProt). Additionally, it incorporates the non-receptor kinase ABL and the collagen receptor DDR2, both of which are involved in cell adhesion and migration. Dysregulation of these kinases through genetic alterations is a hallmark of diverse malignancies, including non-small cell lung cancer, renal cell carcinoma, and chronic myeloid leukemia (PubMed: 21075914). Multi-kinase inhibitors (MKIs) like ponatinib and lenvatinib are designed to target these proteins simultaneously to disrupt multiple signaling nodes and overcome resistance mechanisms (PubMed: 22761451). However, the broad pharmacological profile of these agents often leads to significant off-target or systemic toxicities, such as hypertension and cardiotoxicity, which are linked to the inhibition of physiologically essential pathways (StatPearls).

Other names

Vascular endothelial growth factor receptor 1/2/3 (VEGFR1/2/3)Fibroblast growth factor receptor 1/2/3/4 (FGFR1/2/3/4)Platelet-derived growth factor receptor alpha/beta (PDGFRα/β)Mast/stem cell growth factor receptor Kit (c-Kit)Hepatocyte growth factor receptor (MET)Proto-oncogene tyrosine-protein kinase receptor Ret (RET)Epidermal growth factor receptor (EGFR)Anaplastic lymphoma kinase (ALK)Abelson murine leukemia viral oncogene homolog 1 (ABL)Discoidin domain receptor 2 (DDR2)Ephrin type-B receptor 4 (EphB4)

Inhibition of the intracellular tyrosine kinase domain by competing with ATP for binding, which prevents autophosphorylation and subsequent activation of downstream signaling pathways such as PI3K/AKT, MAPK/ERK, and STAT (PubMed: 22761451).