Anticancer opportunities at every stage of chemokine function. (November 2021)

• Record Type: Journal Article
• Authors: Ortiz Zacarías, Natalia V.; Bemelmans, Martijn P.; Handel, Tracy M.; de Visser, Karin E.; Heitman, Laura H.
• Is Part Of: Trends in pharmacological sciences. Volume 42:Number 11(2021)
• Page Start: 912
• Page End: 928
• Publication Date: 2021-11
• Subjects: cancer -- chemokines -- chemokine receptors -- glycosaminoglycans -- G protein-coupled receptors; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2021.08.001
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : 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. Highlights: The chemokine system has emerged as a relevant target in immune-oncology, with roles in most hallmarks of cancer. Therapeutic targeting of this system can be achieved by interfering with chemokines, chemokine receptors, or glycosaminoglycans. Many therapies aimed at the chemokine system are currently under clinical oncological investigation, including monoclonal antibodies targeting chemokines and their receptors, glycomimetics, and various peptides or small-molecule antagonists for chemokine receptors. Other strategies showed preclinical anticancer value and appear poised for clinical testing, including nanobodies, small-molecule chemokine inhibitors, engineered chemokines, pepducins, siRNA, and biased ligands. The emergence of chemokine receptor antagonists with novel mechanisms of action may prove more effective in the clinic.