scholarly journals Lenvatinib in combination with golvatinib overcomes hepatocyte growth factor pathway‐induced resistance to vascular endothelial growth factor receptor inhibitor

2014 ◽  
Vol 105 (6) ◽  
pp. 723-730 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Tomohiro Matsushima ◽  
Satoshi Kawano ◽  
Youya Nakazawa ◽  
Yu Kato ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Induced Resistance ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth ◽  
Receptor Inhibitor

scholarly journals Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors Which Suppresses Mouse Laser-Induced Choroidal Neovascularization

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xiaoli Zhang ◽  
Manhui Zhu ◽  
Laiqing Xie ◽  
Xiaodong Sun ◽  
Jiaowen Xu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Choroidal Neovascularization ◽  
Growth Factor Receptor ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Hepatocyte Growth Factor Receptor ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

Choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries and is particularly associated with age-related macular degeneration (AMD). Cabozantinib (CBZ) hinders the activation of multiple receptor tyrosine kinases involved in tumor angiogenesis, such as hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). We aimed to investigate the role and mechanism of CBZ in a mouse laser-induced CNV model. In zebrafish embryos, CBZ perturbed intersegmental vessel (ISV) formation without obvious neurodevelopment impairment. In the mouse laser-induced CNV model, phosphorylated hepatocyte growth factor receptor (p-MET) and phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2) were increased in the CNV region. CBZ intravitreal injection or oral gavage alleviated CNV leakage and the CNV lesion area without obvious intraocular toxicity, as well as disturbed the phosphorylation of MET and VEGFR2. Additionally, CBZ downregulated the expression of the hepatocyte growth factor (HGF) with no effect on the expression of the vascular endothelial growth factor (VEGF). CBZ downregulated HGF, p-MET, and p-VEGFR2 expressions in vitro, as well as inhibited the proliferation, migration, and tube formation of b-End3 cells. In summary, CBZ alleviates mouse CNV formation possibly via inhibiting the activation of MET and VEGFR2. The findings provide a novel potential therapy method for CNV patients.

scholarly journals Genetic Basis and Therapies for Vascular Anomalies

2021 ◽  
Vol 129 (1) ◽  
pp. 155-173 ◽  
Author(s):  
Angela Queisser ◽  
Emmanuel Seront ◽  
Laurence M. Boon ◽  
Miikka Vikkula
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathways ◽  
Growth Factor Receptor ◽  
Vascular Anomalies ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited and somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinases), HGF (hepatocyte growth factor)/c-Met (hepatocyte growth factor receptor), and VEGF (vascular endothelial growth factor) A/VEGFR (vascular endothelial growth factor receptor) 2 cascades has led to the evaluation of tailored strategies with preexisting cancer drugs that interfere with these signaling pathways. The era of theranostics has started for the treatment of vascular anomalies. Registration: URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2015-001703-32.

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