Anticancer opportunities at every stage of chemokine function

The chemokine system, comprising 48 chemokines and 23 receptors, is critically involved in several hallmarks of cancer. Yet, despite extensive efforts from the pharmaceutical sector, only two drugs aimed at this system are currently approved for clinical use against cancer. To date, numerous pharmacological approaches have been developed to successfully intervene at different stages of chemokine function: (i) chemokine availability; (ii) chemokine-glycosaminoglycan binding; and (iii) chemokine receptor binding. Many of these strategies have been tested in preclinical cancer models, and some have advanced to clinical trials as potential anticancer therapies. Here we will review the strategies and growing pharmacological toolbox for manipulating the chemokine system in cancer, and address novel methods poised for future (pre)clinical testing.