Anti-angiogenesis Therapy and Strategies for Integrating It with Adjuvant Therapy

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Abstract

The growth of tumors above about 1 mm in diameter requires angiogenesis, the development of a new blood supply, from pre-existing vasculature (Folkman 1990). This applies to both the primary and secondary lesions. Angiogenesis is also essential for systemic metastasis, and it has recently been shown that it is essential for local invasion (Skobe et al. 1997). Normal vasculature is quiescent and each endothelial cell divides only once in 10 years, apart from the endometrial and ovarian angiogenesis during the menstrual cycle and during wound healing. In human tumors the number of dividing endothelial cells may be 50 times greater than in normal tissue. These vessels are leaky, have upregulated vascular growth factor receptors and cell adhesion molecules and are in a procoagulant state. Thus they provide a new therapeutic target with many factors differently expressed between tumor and normal endothelium. This review describes some of the angiogenic pathways and discusses how emerging anti-angiogenic drugs can be integrated into adjuvant trials.