Vascular endothelial growth factor receptor (VEGFR), Tropomyosin receptor kinase A (TrkA), Tropomyosin receptor kinase B (TrkB), and Hepatocyte growth factor receptor (c-Met) (VEGFR/TrkA/TrkB/MET)

The target profile consisting of Vascular Endothelial Growth Factor Receptor (VEGFR), Tropomyosin receptor kinases A and B (TrkA/B), and the Hepatocyte Growth Factor Receptor (c-Met) represents a cluster of receptor tyrosine kinases (RTKs) that are critical drivers of oncogenesis and tumor maintenance [1, 2, 10]. VEGFR is a key regulator of angiogenesis, promoting the formation of new blood vessels to support tumor growth and metastasis [9, 10]. TrkA and TrkB are neurotrophin receptors that promote cell survival and proliferation; their dysregulation through gene fusions or overexpression is a known driver in various solid tumors [11, 12]. c-Met is the receptor for hepatocyte growth factor and plays a pivotal role in cell motility, invasion, and the development of resistance to other tyrosine kinase inhibitors [1, 3, 10]. This specific combination of targets is often addressed by multi-kinase inhibitors to achieve a synergistic effect by blocking both tumor-intrinsic growth and the supportive tumor microenvironment [2, 11]. Drugs like sitravatinib and cabozantinib target this quartet to treat advanced malignancies, including non-small cell lung cancer and renal cell carcinoma [4, 7, 11]. Simultaneous inhibition of these receptors helps to prevent the activation of bypass signaling pathways that typically lead to drug resistance [2, 3]. Clinical development of agents targeting this profile focuses on patients with specific genetic alterations, such as MET amplification or NTRK fusions [11, 12]. Safety profiles for drugs hitting these targets often include class-effect toxicities such as hypertension and gastrointestinal distress [4, 9]. Overall, this multi-target approach represents a sophisticated strategy in precision oncology to tackle complex, heterogeneous tumors.

Other names

VEGFR/Trk/MET profileVEGFR-TrkA-TrkB-METMulti-kinase target profile (VEGFR, TrkA, TrkB, MET)

Inhibition of the intracellular tyrosine kinase domains of VEGFR, TrkA, TrkB, and MET, thereby blocking downstream signaling pathways (e.g., MAPK/ERK, PI3K/AKT) involved in tumor growth, angiogenesis, and immune evasion [1, 2, 11].