Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncologyclinic

Abstract

The words ‘side effect’ usually evoke a mixture of fear and anxiety in cancer patients receiving chemotherapy. But, as it turns out, not all side effects are necessarily harmful, or even undesirable. While the collateral damage inflicted upon the dividing bone marrow progenitors, gut mucosal cells or hair follicle cells by DNA damaging or microtubule inhibiting agents is certainly undesirable, the same cannot always be said of the damage inflicted on endothelial cells present in a tumor’s growing neovasculature. A proportion of these cells are dividing at any given time, making them, at least in theory, sensitive to drugs which preferentially damage or destroy cycling cells [1]. Polverini’s group first reported anti-angiogenic effects mediated by conventional cytotoxic anticancer drugs as long ago as 15 years, and since then most common anticancer chemotherapeutic agents, belonging to all major classes, have been shown to be capable of inhibiting angiogenesis [2]. This prompted George Sledge and colleagues recently to suggest the notion of ‘redefining’ chemotherapeutic drugs as anti-angiogenics [3].