Tumour angiogenesis and response to radiotherapy

The important role of angiogenesis as a predictive factor of response to cytotoxic and radiation therapy has been recently raised. Poor tumour oxygenation is a well recognised feature related to radio-resistance. Since the vascular density is linked to the availability of oxygen and drugs to the tumoural stroma, poor density should be a potent marker of reduced blood perfusion and, therefore, hypoxia and low drug intratumoural concentration. On the other hand, high vascular density and angiogenic ability of cancer is not synonymous with high blood flow since the geometry of the vascular/epithelial component distribution, vascular collapse due to increased interstitial blood pressure, or non-functional vasculature due to an immature structure of the vessels may not allow the establishment of an adequate blood flow, which results in tissue hypoxia. Moreover, activation of angiogenic pathways confer a cancer cell proliferation/apoptosis advantage and trigger an angiogenic regeneration process during fractionated radiotherapy or between the courses of chemotherapy, resulting in rapid tumour re-growth and failure of radiotherapy due to reasons independent of hypoxia and blood flow. The present study reviews the literature on angiogenesis and radiotherapy and suggests a classification of tumours according to their angiogenic ability, which could become a useful tool for the identification of sub-groups of patients that could benefit from specific radiotherapy schedules or combination regimens with cytotoxic and anti-angiogenic compounds.