[Angiogenesis and lung cancer]

Abstract

Inhibition of specific processes essential for tumour vascular development is actually one of the key strategies for treatment of lung cancer, for which angiogenesis is consistently predictive of a poor prognosis. The most promising agents target the vascular endothelial growth factor (VEGF) pathway, either by preventing VEGF-receptor binding as bevacizumab or inhibiting downstream receptor signaling in endothelial cells. Combination of bevacizumab with standard first-line chemotherapy in non-small cell lung cancer demonstrates a significant survival advantage comparing to chemotherapy alone, which provides the "proof of concept" for inhibition of angiogenesis in lung cancer. Development of small molecules inhibiting tyrosine kinase activity of VEGF-receptors is ongoing; many of them showed a single-agent activity but their most likely use will be in combination with chemotherapy or biological agents. Toxicity issues are of concern with the occurrence of fatal pulmonary hemorrhage after cavitation and necrosis of primary tumour, which requires appropriate selection of patients before treatment. A better understanding of the complex process of angiogenesis and of surrogate markers of treatment effect will improve our ability to design more effective therapies.