Chemokine receptors as targets for cancer therapy

Chemokines and their receptors play critical roles in leukocyte trafficking during inflammatory processes. Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse of roles in cancer growth, cancer metastasis, cancer angiogenesis, or the composition of the cancer microenvironment. Preclinical models of cancer indicate that cancer antagonists, most notably those for CXCR4, can block cancer growth either directly or by altering the cancer stroma. Highthroughput screening methods to identify effective CKR antagonists have been developed, but specificity, potency, and drug-delivery of validated candidate compounds remain issues that result in the clinical failure of many initially promising candidates. The recent approval of a CCR5 receptor antagonist in HIV suggests that safe, effective small molecular antagonists for other CKRs may not be far away. There is still a clear need to extend our understanding of the signalling pathways by which CKRs facilitate cancer processes. Because of the role of CKRs in cancer cell survival, the combination of CKR antagonists with traditional chemotoxic agents or with immunotherapy is an alluring strategy since this increases the specificity of treatment to the cancer and potentially limits additional systemic side effects.