Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 4:14:1307860.
doi: 10.3389/fphar.2023.1307860. eCollection 2023.

Recent advances of anti-angiogenic inhibitors targeting VEGF/VEGFR axis

Lei Wang #  1   2 , Wang-Qing Liu #  3 , Sylvain Broussy #  3 , Bingnan Han  2 , Hongming Fang  1
Affiliations
Review

Recent advances of anti-angiogenic inhibitors targeting VEGF/VEGFR axis

Lei Wang et al. Front Pharmacol. .

Abstract

Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20 years, many anti-angiogenic drugs have been developed based on VEGF/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China.

Keywords: VEGF; VEGFR; angiogenesis; anti-angiogenic; inhibitors.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
VEGFR activation by the VEGF family of growth factors; and resulting downstream signaling pathways to angiogenesis and lymphangiogenesis.
FIGURE 2
FIGURE 2
Marketed drugs targeting the VEGF/VEGFR axis and its downstream signaling pathway.
FIGURE 3
FIGURE 3
Macromolecular drugs targeting the extracellular compartment of the VEGF/VEGFR axis for anticancer and ocular therapies.
See this image and copyright information in PMC

References

    1. Aghajanian C., Bell-Mcguinn K. M., Burris H. A., 3rd, Siu L. L., Stayner L. A., Wheler J. J., et al. (2018). A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors. Invest. New Drugs 36, 1016–1025. 10.1007/s10637-018-0591-z - DOI - PMC - PubMed
    1. Al-Obeidi F. A., Wu J. J., Lam K. S. (1998). Protein tyrosine kinases: structure, substrate specificity, and drug discovery. Biopolymers. 47, 197–223. 10.1002/(SICI)1097-0282(1998)47:3<197::AID-BIP2>3.0.CO;2-H - DOI - PubMed
    1. Al-Salama Z. T., Keating G. M. (2016). Cabozantinib: a review in advanced renal cell carcinoma. Drugs 76, 1771–1778. 10.1007/s40265-016-0661-5 - DOI - PubMed
    1. Al-Salama Z. T., Syed Y. Y., Scott L. J. (2019). Lenvatinib: a review in hepatocellular carcinoma. Drugs 79, 665–674. 10.1007/s40265-019-01116-x - DOI - PubMed
    1. Alshangiti A., Chandhoke G., Ellis P. M. (2018). Antiangiogenic therapies in non-small-cell lung cancer. Curr. Oncol. 25, S45–S58. 10.3747/co.25.3747 - DOI - PMC - PubMed

LinkOut - more resources