Vascular endothelial growth factor (VEGF), a survival factor for tumour cells: implications for anti-angiogenic therapy.
Angiogenesis is central to both the growth and metastasis of solid tumours. Anti-angiogenic strategies result in blood vessel regression accompanied by tumour cell apoptosis. Radiotherapy and many chemotherapeutic agents kill tumours by inducing apoptotic cell death. We propose that, in addition to its role as an angiogenic factor, vascular endothelial growth factor (VEGF) can act as a survival factor for tumour cells protecting them from apoptosis. Thus anti-angiogenics, in particular those directed against VEGF, have multiple anti-tumour effects. We suggest that anti-VEGF strategies prevent vessel growth and block a tumour cell survival factor, VEGF, rendering tumour cells more sensitive to chemotherapy and radiotherapy. In addition, as chemotherapy and radiotherapy have been shown to increase VEGF expression, anti-VEGF strategies may overcome therapy- induced tumour cell resistance.
Harmey
Judith H
JH
Department of Surgery, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. jharmey@rcsi.ie
Bouchier-Hayes
David
D
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D008222:Lymphokines / Q000378:metabolism* / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors