Cited by 219Angiogenesis and VEGF in CancerLymphatic System and DiseasesCancer Mechanisms and Therapy

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Vascular Endothelial Cell Growth Factor (VEGF), An Emerging Target for Cancer Chemotherapy

Shinkaruk, S., Bayle, M., Lain, G., Deleris, G.·2003·Current Medicinal Chemistry-Anti-Cancer Agents

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Abstract

Angiogenesis is a process of development and of growth of new capillary blood vessels from pre-existing vessels. When pathological, it contributes to the development of numerous types of tumors, and the formation of metastases. In order to grow, carcinoma need new blood vessels to form so that they can feed themselves. Therefore, nowadays the concept according to which the development of cancer is angiogenesis dependent is generally recognized. This concept makes the control of tumoral angiogenesis one of the promising therapeutic ways in cancerology. The transition from the latent phase to the invasive and metastatic phase of a cancer is linked to what is called the angiogenic switch. It implies complex cellular and molecular interactions between cancerous cells, endothelial cells and the components of the extra-cellular matrix and namely the existence of specific proteins secreted by the tumoral cells able to stimulate the proliferation of capillary endothelial cells. Among them, VEGF, Vascular Endothelial Growth Factor was found in several types of tumors. It has shown a tumoral angiogenic activity in vitro and in vivo, and thus is a privileged target for the control of angiogenesis in an anti-tumoral goal. The role of VEGF in tumoral angiogenesis has been extensively studied. It has been proved to undergo as well autocrine as paracrine stimulation of tumoral angiogenesis. During the last few years, several members of the VEGF family have been described namely the VEGF-A, B, C, D, E and placenta growth factor (PlGF) among which VEGF-A (121 aminoacids) plays a role of prime importance in angiogenesis. VEGF is a 45 kDA glycoprotein, homodimeric, basic, and able to bind heparin. The three-dimensional structure of VEGF has been recently determined, by X-rays diffraction, and NMR spectroscopy. The different forms of the VEGF bind to receptors that exhibit a tyrosine-kinase activity (RTK). The specific action of the VEGF on the endothelial cells is mainly regulated by two types of RTK of the VEGF family, VEGFR1, or Flt-1, and VEGFR2, or KDR/Flk-1. Mutagenesis studies have shown that only a small number of VEGF residues are important and essential for the binding with RTK. Data described to date from the studies of VEGF/RTK interactions agree to the hypothesis that KDR receptor is the main human receptor responsible for the VEGF activity in both physiological and pathological vascular development, and VEGF-KDR signalling pathway has been validated as a priority target for the development of anti- and pro- angiogenic agents. Therefore angiogenesis mediated by VEGF constitutes a new target for anti-cancer therapy which has explored through different ways of intervention aiming at the blocking of the tumoral angiogenesis. The main ones are: -Struggle against the stroma degradation and invasion by the neo-vessels -Inhibition of activated endothelial cells. -Inhibition of angiogenic factors production and of their receptors. -Inhibition of the VEGF signal pathway, by peptides blocking the bond between VEGF and its receptors through the inhibition of intracellular transduction of VEGF signal. In conclusion, this bibliographic study allows to situate works of medicinal chemistry in the context of present knowledge concerning the vascular endothelial growth factor (VEGF) and its role in angiogenesis.

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“The VEGF family has at least seven members, and VEGF-A is a key player in angiogenesis [2,3].”
Background
Noninvasive characterization of the healthy human manubrium using diffuse optical spectroscopies
Farzam, P., Lindner, C., Weigel, U. M., et al. (2014) · Physiological Measurement · doi:10.1088/0967-3334/35/7/1469 · Cited by 35
Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis
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“31 Of these, VEGF-A (initially known as vascular permeability factor) was the first to be discovered and exists as four isoforms (VEGF-A121, VEGF-A165, VEGF-A189, VEGF-A206) 32 generated by variable splicing of the VEGF-A gene.”
Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression
Chen, M., Lin, M., & Wang, X. (2017) · Oncology Reports · doi:10.3892/or.2017.6110 · Cited by 35
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Patsouras, D., Papaxoinis, K., Kostakis, A. I., et al. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3259 · Cited by 34
The potential role of nintedanib in treating colorectal cancer
Rossi, A., Latiano, T. P., Parente, P., Chiarazzo, C., Limosani, F., Maggio, G. D., & Maiello, E. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1346086 · Cited by 32
“VEGFR-3 is activated by VEGF-C and VEGF-D and has been found to be primarily associated with lymphangiogenesis [14,15].”
Background
Up-regulation of soluble vascular endothelial growth factor receptor-1 prevents angiogenesis in hypertrophied myocardium
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Pondering the puzzle of PML (promyelocytic leukemia) nuclear bodies: Can we fit the pieces together using an RNA regulon?
Borden, K. L. B. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.06.005 · Cited by 34
“Note that increased VEGF levels correlate with increased metastasis [112,113].”
Background
Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial
Hou, Z., Zhu, K., Yang, X., Chen, P., Zhang, W., Cui, Y., Zhu, X., Song, T., Li, Q., Li, H., et al. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-2990 · Cited by 31
“Vascular endothelial growth factor (VEGF) signaling is considered to be the main pathway responsible for angiogenesis (8-11), with VEGFR2 being a critical mediator of VEGF-induced angiogenic signaling (12).”
Background
Metastasis models: the green fluorescent revolution?
Paris, S. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh219 · Cited by 31
Indirubin derivative E804 inhibits angiogenesis
Shin, E.-K., & Kim, J. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-164 · Cited by 30
“Accordingly, the VEGF signaling pathway has become an important target for anti-cancer treatment and many approaches have been developed to inhibit this pathway [8,9].”
Background
Hepatocellular carcinoma cells cause different responses in expressions of cancer‐promoting genes in different cancer‐associated fibroblasts
Lin, Z., & Chuang, W. (2012) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2012.08.012 · Cited by 31
“Besides PGK1 gene, HCC38/KMUH cancer cells only upregulated APLN, LOXL2, and VEGFA genes and HCC24/KMUH cancer cells only up-regulated FGF2 gene in F26/KMUH CAFs.”
BackgroundInfluential
Biochemical and Structural Analysis of the Binding Determinants of a Vascular Endothelial Growth Factor Receptor Peptidic Antagonist
Gautier, B., Gonçalves, V., Diana, D., Stasi, R. D., Teillet, F., Lenoir, C., Huguenot, F., Garbay, C., Fattorusso, R., D’Andrea, L. D., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm1002167 · Cited by 34
NAT10 promotes osteogenic differentiation of periodontal ligament stem cells by regulating VEGFA-mediated PI3K/AKT signaling pathway through ac4C modification
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“VEGF has a very high affinity and can directly or indirectly promote angiogenesis [26].”
Background
Discovery of novel tricyclic pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amine derivatives as VEGFR-2 inhibitors
Aziz, Y. M. A., Said, M. M., Shihawy, H. A. E., et al. (2015) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2015.03.004 · Cited by 29
Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation
Heffelfinger, S. C., Yan, M., Gear, R. B., Schneider, J., LaDow, K., & Warshawsky, D. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700128 · Cited by 29
Novel investigational vascular endothelial growth factor (VEGF) receptor antagonists for psoriasis
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“[22] VEGF specifically stimulates mitosis in endothelial cells, increases vascular permeability, and contributes to chemotaxis and activation of monocytes.[19,21,23] VEGF ligands selectively bind to VEGFRs, which are tyrosine kinases (TK)s.”
Background
Discovering Small Molecule Ligands of Vascular Endothelial Growth Factor That Block VEGF–KDR Binding Using Label-Free Microarray-Based Assays
Landry, J. P., Fei, Y., Zhu, X. D., Ke, Y., Yu, G., & Lee, P. (2013) · Assay and Drug Development Technologies · doi:10.1089/adt.2012.485 · Cited by 27
“We used plated sets from NCI/DTP with a total of 7,961 compounds: (1) a Challenge set with 57 compounds (10 mM); (2) a Natural Products set with 235 compounds (10 mM); (3) a Structural Diversity set with 1,990 compounds (10 mM); (4) a Mechanistic Diversity set with 879 compounds (1 mM); and (5) an Open set with 4,800…”
Method
Chitosan sulfate inhibits angiogenesis via blocking the VEGF/VEGFR2 pathway and suppresses tumor growth in vivo
Li, Y., Wang, W., Zhang, Y., Wang, X., Gao, X., Yuan, Z., & Li, Y. (2019) · Biomaterials Science · doi:10.1039/c8bm01337c · Cited by 28
Early diagnosis and straight forward surgery of an asymptomatic primary angiosarcoma of the kidney led to long‐term survival
Akkad, T., Tzankov, A., Pelzer, A. E., et al. (2006) · International Journal of Urology · doi:10.1111/j.1442-2042.2006.01490.x · Cited by 26
Advances in the Mechanism of Luteolin against Hepatocellular Carcinoma Based on Bioinformatics and Network Pharmacology
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“Angiogenesis, the process of forming new blood vessels and blood supply structures, is one of the important mechanisms of tumor growth and metastasis [73].”
Background
VEGF-ERCNN: A deep learning-based model for prediction of vascular endothelial growth factor using ensemble residual CNN
Ali, F., Khalid, M., Masmoudi, A., et al. (2024) · Journal of Computational Science · doi:10.1016/j.jocs.2024.102448 · Cited by 23
Is There a Role for Treating Inflammation in Moyamoya Disease?: A Review of Histopathology, Genetics, and Signaling Cascades
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“VASCULAR ENDOTHELIAL GROWTH FACTOR Vascular endothelial growth factor is a 45-kD homodimeric, basic glycoprotein that requires association with heparin in order to function (27).”
Background
Raf-Induced Vascular Endothelial Growth Factor Augments Kaposi's Sarcoma-Associated Herpesvirus Infection
Hamden, K. E., Ford, P. W., Whitman, A. G., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.23.13381-13390.2004 · Cited by 23
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Background
Perspectives in PML: a unifying framework for PML function
Borden, K. L. B. (2009) · Frontiers in bioscience · doi:10.2741/3258 · Cited by 24
“Increased VEGF levels correlate with increased metastatic disease (91, 92).”
Background
Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome
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Identification of novel cytokine biomarkers of hexanal exposure associated with pulmonary toxicity
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The influence of vascularization of transplanted processed allograft nerve on return of motor function in rats
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Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells
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Antiangiogenetic effects of anthranoids from Alternaria sp., an endophytic fungus in a Thai medicinal plant Erythrina variegata
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Expression of cyclo-oxygenase 1 and 2, prostaglandin E synthase and transforming growth factor β1, and their relationship with vascular endothelial growth factors A and C, in primary adenocarcinoma of the small intestine
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“VEGF promotes vascular endothelial growth and mediates vascular permeability, thereby promoting tumor progression and metastatic diffusion [32].”
Background
miR‑140‑5p regulates cell migration and invasion of non‑small cell lung cancer cells through targeting VEGFA
Yang, P., Xiong, J., Zuo, L., et al. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9291 · Cited by 19
“VEGF is a member of the platelet-derived growth factor family, which includes VEGFA, VEGFB, VEGFC, VEGFD and VEGFE (10).”

Authors: Shinkaruk, S., Bayle, M., Lain, G., & Deleris, G.
Affiliations: Inserm (FR)
ORCID: Shinkaruk, S.
Venue: Current Medicinal Chemistry-Anti-Cancer Agents
Publisher: Bentham Science Publishers Ltd.
Published: 2003-03-01
Volume: 3
Issue: 2
Pages: 95-117
ISSN: 1568-0118 (ISSN-L)
DOI: 10.2174/1568011033353452
OpenAlex: W2070230256
Cited by: 219
References: 0
Citations by year: 2026: 3 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 14 · 2017: 12 · 2016: 11 · 2015: 13 · 2014: 15 · 2013: 10 · 2012: 11
FWCI: 3.68
Type: journal article
Language: en
Open access: closed
Locations: Anti-Cancer Agents in Medicinal Chemistry (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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Keywords: vascular endothelial growth factor, angiogenesis, tumor angiogenesis, anti-angiogenic cancer therapy, VEGF receptors, VEGFR2, VEGFR1, VEGF-A, VEGF family, angiogenic switch, metastasis, autocrine and paracrine signaling, receptor tyrosine kinase, anti-VEGF therapy, VEGF inhibitors
MeSH terms: Animals, Endothelium, Vascular, Humans, Lymphokines, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Endothelial Growth Factors, Paracrine Communication, Angiogenesis Inhibitors, Intercellular Signaling Peptides and Proteins, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A

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Vascular Endothelial Cell Growth Factor (VEGF), An Emerging Target for Cancer Chemotherapy

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