Antineovascular therapy, a novel antiangiogenic approach

Angiogenesis is a crucial event in tumour growth, since the growth of tumour cells depends on the supply of essentials such as oxygen and nutrients. Therefore, suppression of angiogenesis is expected to show potent therapeutic effects on various cancers. Additionally, this 'antiangiogenic therapy' is thought not only to eradicate primary tumour cells, but also suppress tumour metastases through disruption of haematogenous metastatic pathways. Tumour dormancy therapy does not aim to disrupt newly formed angiogenic vessels but aims to inhibit further formation of neovessels through inhibiting certain processes of angiogenesis. This raises a question of whether or not these antiangiogenic agents bring complete cure of tumours as complete cut-off of oxygen and nutrients is not expected by the treatment with these agents. This paper will review a novel antiangiogenic therapy, antineovascular therapy (ANET). ANET is categorised in antiangiogenic therapy but is different from tumour dormancy therapy using conventional angiogenic inhibitors: ANET aims to disrupt neovessels rather than to inhibit neovessel formation. ANET is based on the fact that angiogenic endothelial cells are growing cells and would be effectively damaged by cytotoxic agents when the agents are effectively delivered to the neovessels. The complete eradication of angiogenic endothelial cells may cause complete cut-off of essential supplies to the tumour cells and lead to indirect but strong cytotoxicity instead of cytostasis caused by the inhibition of angiogenesis. For the purpose of ANET, an angiogenic vasculature-targeting probe has been developed, by which cytotoxic anticancer agents are actively delivered to the angiogenic endothelial cells by using drug delivery system (DDS) technology. Another way to damage newly formed vessels by cytotoxic agents is achieved by metronomic-dosing chemotherapy. This chemotherapy shifts the target of chemotherapeutic agents from tumour cells to angiogenic endothelial cells by selective dosing schedule. Similarly, the shift of target from tumour cells to angiogenic endothelial cells enhanced therapeutic efficacy of cancer photo-dynamic therapy (PDT): in this antiangiogenic PDT, photosensitizers are delivered more to neovessel endothelial cells than to tumour cells. These therapeutic strategies would be clinically applied in the future.