6. Inducing angiogenesis

All cancers require a functional vascular network to ensure continued growth and will be unable to grow beyond 1 mm³ without stimulating the development of a vascular supply. Tumours require sustenance in the form of nutrients and oxygen as well as an ability to evacuate metabolic waste products and carbon dioxide. This requires the development of new blood vessels, which is termed angiogenesis (Figure 6.1).

In an adult, the normal vasculature is largely quiescent, but as part of certain physiological processes, such as wound healing and female reproductive cycling, angiogenesis is transiently turned on. Blood vessels produced by tumour-mediated angiogenesis are abnormal and do not follow the normal patterns of vascular development. They are characterised by:

• precocious capillary sprouting;
  
• increased vessel branching;
  
• distorted and enlarged vessels;
  
• microhaemorrhage and leakiness;
  
• abnormal levels of endothelial cell proliferation and apoptosis.

Angiogenesis is dependent on the production of angiogenic growth factors, of which vascular endothelial growth factor (VEGF) and platelet-derived endothelial growth factor (PDGF) are the best characterised. During tumour progression, an angiogenic switch is activated and remains on, causing normally quiescent vasculature to continually sprout new vessels that help sustain expanding tumour growth. Angiogenesis is governed by a balance of proangiogenic stimuli and angiogenesis inhibitors, such as TSP-1, which binds to transmembrane receptors on endothelial cells and evokes suppressive signals.

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Presenting problems in a patient with cancer Paraneoplastic syndromes Principles of radiotherapy The role of multidisciplinary teams Cervical cancer to case studies

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