The Potential of Combination Therapies and Patient Stratification to Improve CCR2 Inhibition Therapeutics.

Abstract

Chemokines and their receptors are the communication mechanism used by cells of the immune system, allowing them to identify and eliminate pathogens and cancerous cells. However, it is becoming clear that chemokines and their receptors are also playing a role in tumor progression and metastasis [1,2]. An example of such coopting is the CCL2-CCR2 axis. The chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) is known to bind the CCR2 receptor on monocytes [3] and attract them to areas of need. What is now clear is that CCR2 levels are high in tumors of a number of cancer types. For example, in bladder cancer, 12 different patient datasets [4] all show that CCL2 expression is higher in the more advanced, muscle invasive disease than the non-muscle invasive disease [5]. In line with this, high CCL2 expression correlates with a worse overall survival in bladder cancer [5]. CCL2 and CCR2 are also associated with disease progression in many other cancer types including breast, ovarian, lung and colon [6,7].