Polymer therapeutics for cancer: Current status and future challenges

Drug delivery systems for cancer therapeutics have revolutionized medicine. Delivery systems have improved the efficacy and reduced the toxicity of current therapies and resulted in the development of new ones. Today, millions of cancer patients have directly benefited from drug delivery systems, and polymers have been at the frontline of these technological advances. Targeted delivery systems of chemotherapeutics to the tumour compartment can be achieved systemically, either passively or actively. Polymer conjugation radically changes the pharmacokinetics of the bound drug, and conjugates with prolonged circulation times target tumours passively via the enhanced permeability and retention (EPR) effect. Polymer conjugates can also be modified with moieties to directly target the tumour cells or the tumour vasculature. In this chapter, we review the successful clinical application of polymer-protein conjugates, and promising clinical results arising from trials with polymer-anticancer-drug conjugates. Over the last decade more than twelve polymer-drug conjugates have entered Phase I/II clinical trial as intravenously injectable anticancer agents. Only one of the polymer conjugates that has reached clinical trial directly targets tumour cells, while another one targets the tumour vasculature. Conjugation to polymers may save the fate of the many promising drug/peptide chemotherapies that fail each year due to high toxicity or poor pharmacokinetics. Yet, these technologies have not been exploited to their full potential. Only a few combinations of a limited number of chemotherapeutic drugs and polymer delivery systems are being tested in clinical and preclinical trials today. Furthermore, genomics and proteomics research is producing novel peptides, proteins and oligonudeotides that lack effective delivery systems. Thus, the full potential for drug delivery systems based on NCEs (new chemical entities), such as "polymer therapeutics", lies ahead.