Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2020 Nov 30;13:12301–12316. doi: 10.2147/OTT.S174149

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2020 Tacconi et al.

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

PMC Copyright notice

Mechanism of action of TKIs used in metastatic RCC. Kinases regulating angiogenesis are frequently overexpressed in RCC, culminating in increased tumour vascular supply. VHL inactivation leads to overexpression of pro-angiogenic factors including VEGF via increased HIFα expression. HIFα is also upregulated via PI3K/mTOR signalling. VEGF binds to VEGFR1/2/3 on endothelial cell surfaces, promoting angiogenesis. Additional cell surface receptors regulating angiogenesis include PDGFR (platelet-derived growth factor receptor), FGFR (fibroblast growth factor receptor), tyrosine-protein kinase MET (hepatocyte growth factor receptor), AXL oncogene (tyrosine-protein kinase receptor UFO) and proto-oncogene tyrosine-protein kinase receptor RET. A range of TKIs have been developed targeting various aspects of these signalling pathways. Adapted by permission from Springer Nature © (2017). Posadas EM, Limvorasak S, Figlin RA. Targeted therapies for renal cell carcinoma. Nat Rev Nephrol. 2017;13(8):496–511.13

Abbreviations: PDGF, platelet-derived growth factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; GAS6, growth arrest-specific protein 6; GDNF, glial cell line-derived neurotrophic factor.