Antiangiogenics and radiotherapy.

Antiangiogenic therapies are one of the fore-runners of the new generation of anticancer drugs aimed at tumour-specific molecular targets. Up until the beginning of this century, the general opinion was that targeted agents should show antitumour activity when used as single agents. However, it has now become clear that much greater improvements in therapeutic activity may be achieved by combining the novel agents with conventional cytotoxic therapies already in use in the clinic. Radiotherapy is currently used to treat half of all cancer patients at some stage in their therapy, although the development of radioresistance is an ongoing problem. It is therefore reasonable to expect that any novel molecularly-targeted agent which reaches the clinic will be used in combination with radiotherapy. The rationale for combining antiangiogenics in particular with radiotherapy exists, as radiotherapy has been shown to kill proliferating endothelial cells, suggesting that inhibiting angiogenesis may sensitise endothelial cells to the effects of radiation. Furthermore, targeting the vasculature may paradoxically increase oxygenation within tumours, thereby enhancing radiotherapy efficacy. In this review we present an update on the use of antiangiogenic methods in combination with radiotherapy.