Cited by 748Angiogenesis and VEGF in CancerLymphatic System and DiseasesVascular Tumors and Angiosarcomas

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Angiogenesis: regulators and clinical applications

Liekens, Sandra, De Clercq, Erik, Neyts, Johan·2001·Biochemical Pharmacology

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Abstract

Angiogenesis is a fundamental process in reproduction and wound healing. Under these conditions, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases and is thought to be indispensable for solid tumor growth and metastasis. The construction of a vascular network requires different sequential steps including the release of proteases from "activated" endothelial cells with subsequent degradation of the basement membrane surrounding the existing vessel, migration of endothelial cells into the interstitial space, endothelial cell proliferation, and differentiation into mature blood vessels. These processes are mediated by a wide range of angiogenic inducers, including growth factors, chemokines, angiogenic enzymes, endothelial specific receptors, and adhesion molecules. Finally, when sufficient neovascularization has occurred, angiogenic factors are down-regulated or the local concentration of inhibitors increases. As a result, the endothelial cells become quiescent, and the vessels remain or regress if no longer needed. Thus, angiogenesis requires many interactions that must be tightly regulated in a spatial and temporal manner. Each of these processes presents possible targets for therapeutic intervention. Synthetic inhibitors of cell invasion (marimastat, Neovastat, AG-3340), adhesion (Vitaxin), or proliferation (TNP-470, thalidomide, Combretastatin A-4), or compounds that interfere with angiogenic growth factors (interferon-alpha, suramin, and analogues) or their receptors (SU6668, SU5416), as well as endogenous inhibitors of angiogenesis (endostatin, interleukin-12) are being evaluated in clinical trials against a variety of solid tumors. As basic knowledge about the control of angiogenesis and its role in tumor growth and metastasis increases, it may be possible in the future to develop specific anti-angiogenic agents that offer a potential therapy for cancer and angiogenic diseases.

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Authors: Liekens, S., De Clercq, E., & Neyts, J.
Affiliations: Rega Institute for Medical Research (BE)
Corresponding author: Liekens, Sandra
ORCID: Liekens, Sandra
Neyts, Johan
Venue: Biochemical Pharmacology
Publisher: Elsevier BV
Published: 2001-02
Volume: 61
Issue: 3
Pages: 253-270
ISSN: 0006-2952 (ISSN-L)
DOI: 10.1016/s0006-2952(00)00529-3
OpenAlex: W2109197670
Cited by: 748
References: 231
Citations by year: 2026: 5 · 2025: 10 · 2024: 11 · 2023: 14 · 2022: 16 · 2021: 22 · 2020: 20 · 2019: 16 · 2018: 17 · 2017: 25 · 2016: 33 · 2015: 39 · 2014: 44 · 2013: 30 · 2012: 28
FWCI: 16.00
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
Keywords: angiogenesis, neovascularization, angiogenesis inhibitors, anti-angiogenic therapy, tumor growth, metastasis, angiogenic factors, endothelial cell migration, basement membrane degradation, endostatin, marimastat, combretastatin A-4, thalidomide, wound healing, reproduction
MeSH terms: Humans, Neoplasms, Neovascularization, Pathologic, Neovascularization, Physiologic, Angiogenesis Inhibitors, Angiogenesis Inducing Agents

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