Vegf-targeted therapy: mechanisms of anti-tumour activity

KEY POINTS * Vascular endothelial growth factor (VEGF) mediates numerous changes within the tumour vasculature, including endothelial cell proliferation, migration, invasion, survival,

chemotaxis of bone marrow-derived progenitor cells, vascular permeability and vasodilation. * There are several approaches to inhibiting VEGF signalling, including neutralization of the

ligand or receptor by antibodies, and blocking VEGF receptor (VEGFR) activation and signalling with tyrosine kinase inhibitors. * VEGF-targeted therapy has been shown to be efficacious as a

single agent in renal cell carcinoma and hepatocellular carcinoma, whereas it is only of benefit when combined with chemotherapy for patients with metastatic colorectal, non-small-cell lung

and metastatic breast cancer. * VEGF-targeted therapy affects numerous cell types within the tumour microenvironment, including endothelial cells, haematopoietic progenitor cells, dendritic

cells and tumour cells. * VEGF-targeted therapy has multiple mechanisms of action that might be dependent on tumour type. * VEGF-targeted therapy affects vascular function (flow and

permeability) in addition to blocking further new blood vessel growth. ABSTRACT Several vascular endothelial growth factor (VEGF)-targeted agents, administered either as single agents or in

combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. VEGF-targeted therapies were initially developed with the notion that they would inhibit

new blood vessel growth and thus starve tumours of necessary oxygen and nutrients. It has become increasingly apparent, however, that the therapeutic benefit associated with VEGF-targeted

therapy is complex, and probably involves multiple mechanisms. A better understanding of these mechanisms will lead to future advances in the use of these agents in the clinic. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS ANGIOGENIC SIGNALING PATHWAYS AND ANTI-ANGIOGENIC THERAPY FOR CANCER Article Open access 11 May 2023 TARGETING THE TUMOUR VASCULATURE: FROM VESSEL

DESTRUCTION TO PROMOTION Article 29 August 2024 THERAPEUTIC PARADIGM OF DUAL TARGETING VEGF AND PDGF FOR EFFECTIVELY TREATING FGF-2 OFF-TARGET TUMORS Article Open access 24 July 2020

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Discovery, Schering-Plough Research Institute, Schering-Plough Corporation, 2,015 Kenilworth, Galloping Hill Road, New Jersey 07033, USA. AUTHORS AND AFFILIATIONS * Departments of Surgical

Oncology and Cancer Biology, Unit 444, University of Texas M.D. Anderson Cancer Center, PO Box 301402, Houston, 77230–1402, Texas, USA Lee M. Ellis & Daniel J. Hicklin Authors * Lee M.

Ellis View author publications You can also search for this author inPubMed Google Scholar * Daniel J. Hicklin View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHORS Correspondence to Lee M. Ellis or Daniel J. Hicklin. ETHICS DECLARATIONS COMPETING INTERESTS Consulting (L.M.E.): ImClone Systems, Genentech Research Support

(L.M.E.): ImClone Systems, Amgen, Sanofi-Aventis Employee of Schering-Plough Corporation (D.J.H.) Ownership of stock in Schering-Plough Corporation (D.J.H.) RELATED LINKS RELATED LINKS

DATABASES NATIONAL CANCER INSTITUTE breast cancer colorectal cancer pancreatic cancer NATIONAL CANCER INSTITUTE DRUG DICTIONARY axitinib bevacizumab endostatin interferon-α oxaliplatin

paclitaxel sorafenib sunitinib TNP-470 FURTHER INFORMATION Angiogenesis inhibitors in clinical trials GLOSSARY * VEGF trap A fully human soluble decoy receptor protein that consists of a

fusion of the second immunoglobulin (Ig) domain of human VEGFR1 and the third Ig domain of human VEGFR2 with the constant region (Fc) of human IgG1. VEGF trap has a high affinity for all

isoforms of VEGFA, as well as PlGF. * Progression-free survival (PFS). The length of time that patients are free from any significant increase in tumour size or development of new tumours.

PFS is measured as the time from start of treatment to the first measurement of cancer growth (by pre-defined criteria). * Vasculogenesis This term is used for the _de novo_ formation of new

blood vessels from haematopoietic progenitor cells and normally takes place during embryogenesis. During tumour angiogenesis, EPCs migrate to sites of tumour growth and differentiate into

tumour endothelial cells participating in new blood vessel growth. * Allogeneic Allogeneic refers to cells or tissues from two different individual sources that are the same strain, but

differ genetically in their major histocompatibility complex. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ellis, L., Hicklin, D. VEGF-targeted

therapy: mechanisms of anti-tumour activity. _Nat Rev Cancer_ 8, 579–591 (2008). https://doi.org/10.1038/nrc2403 Download citation * Published: 03 July 2008 * Issue Date: August 2008 * DOI:

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