The chemokine network: a target in cancer biology?

Chemokine gradients are central to the movement of cells in both homeostatic and pathological processes. Most cancers express a complex array of chemokines that influence the local microenvironment through recruitment of stromal cells and by stimulating angiogenesis. Recently, the discovery of chemokine receptors on tumor cells has led to speculation that the chemokine system may be involved in cancer cell growth and survival, and possibly the development of site-specific spread. Understanding the networks of chemokines and their receptors in cancer will enable manipulation of this system. Both chemokines and their receptors represent targets for therapeutic intervention either with antibodies or small molecule antagonists. However, due to the complexity of the system, and the number of chemokines and receptors that are also expressed by normal cells, issues remain concerning whether systemic or local drug delivery are preferable and whether the redundancy of the system will compensate if one chemokine or receptor is targeted. Nevertheless, efficacy has been demonstrated in a number of experimental models. By targeting this network, it may be possible to generate anti-tumor immune responses by altering the chemokine and/or leukocyte balance in tumors; alternatively, chemokine/chemokine receptor-expressing cancer cells could be directly targeted.