Chemokines and their receptors regulate the trafficking of leukocytes in hematopoiesis and
inflammation, and thus are fundamental to the immune integrity of the host. In parallel, members of the
chemokine system exert a large variety of functions that dictate processes of
cancer development and progression.
Chemokines can act as pro-tumoral or anti-tumoral regulators of
malignancy by affecting cells of the tumor microenvironment (leukocytes, endothelial cells, fibroblasts) and the
tumor cells themselves (migration, invasion, proliferation, resistance to
chemotherapy). Several of the
chemokines are generally skewed towards the
cancer-promoting direction, including primarily the CCR5-CCL5 (
RANTES) and the CXCR4-CXCL12 (SDF-1) axes. This review provides a general view of
chemokines and
chemokine receptors as regulators of
malignancy, describing their multi-faceted activities in
cancer. The
tumor-promoting activities of the CCR5-CCL5 and CXCR4-CXCL12 pathways are enlightened, emphasizing their potential use as targets for personalized
therapy. Indeed, novel blockers of
chemokines and their receptors are constantly emerging, and two
chemokine receptor inhibitors were recently approved for clinical use:
Maraviroc for CCR5 and
Plerixafor for CXCR4. The review addresses ongoing pre-clinical and clinical trials using these modalities and others in
cancer. Then, challenges and opportunities of personalized
therapy directed against
chemokines and their receptors in
malignancy are discussed, demonstrating that such novel personalized
cancer therapies hold many challenges, but also offer hope for
cancer patients.