The polyamine transport system as a target for anticancer drug development

The vast majority of anticancer drugs in clinical use are limited by systemic host toxicity due to their non-specific side effects. These shortcomings have led to the development of tumour specific drugs which target a single-deregulated pathway or over expressed receptor in cancer cells. Whilst this approach has achieved clinical success, we have also learnt that targeting a single entity in cancer is rarely curative due to the large number of deregulated pathways, receptors and kinases which are also present, in addition to the target. An attractive alternative to improve targeting would be to harness the already established activity of known anticancer drugs by attaching them to a molecule that is transported into cancer cells via a selective transport system. One possibility for this approach is the polyamine pathway. This review provides a brief overview of the polyamine pathway and how, over the years, it has proved an exciting target for the development of novel anticancer agents. However, the focus of this article will be on the properties of the polyamine transport system and how these features could potentially be exploited to develop a novel and selective anticancer drug delivery system.