Angiogenesis Inhibitors: Current & Future Directions

Shaker   A.   Mousa; Ahmed   S.   Mousa

doi:10.2174/1381612043453531

Abstract

The field of angiogenesis modulation is at a major crossroad. A tremendous advancement in basic science in this field is providing an excellent support for the concept, which is in contrast to a lack of strong clinical support to date. With regard to the large gap between experimental data and clinical data, the best model of human malignancy is in human cancer patients and the best model of human ocular angiogenesis-mediated disorders such as diabetic retinopathy (DR) and age related macular degeneration (AMD) is in human RD and AMD patients. Additionally, clinical outcomes should include benefit / risk ratios, hard end points (mortality and quality of life as opposed to increased microvascular density with pro-angiogenic agents or tumor size reduction with anti-angiogenesis agents) as well as cost effectiveness. Experimental models should be used to provide guidance, placebo effect, comparative data, and mechanistic understanding as opposed to being used for expected clinical efficacy. We also have to understand existing strategies and how angiogenesis modulation can add further value (i.e. not to replace existing strategy but rather improve efficacy / safety). Recent investigation defined numerous strategies in the modulation of angiogenesis. Those strategies are driven from haemostatic, fibrinolytic, cell adhesion molecules, extracellular matrix, growth factors, and other endogenous systems involved in the modulation of angiogenesis.

Keywords: Angiogenesis, matrix, fibrinolytic, endogenous, haemostatic