Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment

Abstract

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Keywords

• breast cancer
• tumor microenvironment
• CCL5
• CCL5/CCR5 axis
• mRNA