Targeting tumours: Developing vector systems

The vast majority of anticancer chemotherapeutic agents in clinical use have a high incidence of adverse side effects as a result of their lack of specificity towards malignant cells. The therapeutic use of these drugs is therefore limited, despite most of them having potent anti-tumour activity in vitro1. The non-specific actions can be overcome by targeting tumour cells more selectively than healthy cells and this is therefore a major challenge facing modern cancer therapy. Ideally, decreased uptake of these agents by healthy cells would not only decrease their associated toxicity, but also lower the dose required to kill the cancer cell. Current approaches to develop tumour-specific drugs are based on targeting a single deregulated pathway or an overexpressed receptor, and there are a number of molecules that successfully validate this strategy. These include monoclonal antibodies, peptides, folic acid, hormones and growth factors. Although demonstrating selective targeting is feasible, few of these agents are useful therapeutically, since most of the drugs have shown modest cell killing activity2. A valuable alternative to enhance drug specificity is to develop vector systems that have an enhanced affinity towards cancer cells. This would enable better use of already established chemotherapeutic agents as a result of preferential uptake and diminished secondary effects on healthy cells. Over the last few years, polyamine backbones have been studied as one such vector system, aiming to take advantage of the polyamine transport system (PTS) in cancer cells for selective delivery of known anticancer drugs. In this article, we describe the basic principles, as well as recent advances regarding this novel approach.