An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer.

ABSTRACT

Chronic inflammation is a major factor in tumor growth and progression. Cancer cells secrete C-X-C chemokine ligand 8 (CXCL8) along with its receptor C-X-C chemokine receptor 1 (CXCR1) and chemokine receptor 2 (CXCR2). It plays a significant role in the activation and trafficking of inflammatory mediators, tumor proliferation and interferes in breast cancer development by controlling cell adhesion, proliferation, migration, and metastasis. This axis also plays a significant role in driving different cancers and melanomas, including breast cancer progression, by controlling stem cell masses. Few small-molecule CXCR1/2 inhibitors and CXCL8 releasing inhibitors have been identified in the past two decades that bind these receptors in their inactive forms and blocks their signaling as well as the biological activities associated with inflammation. Inhibitors of certain inflammatory molecules are projected to be more efficient in different inflammatory diseases. Preclinical trials indicate that patients may be benefitted from combined treatment with targeted drugs, chemotherapies, and immunotherapies. Thus, targeting the CXCL8-CXCR1/2 signaling axis in breast cancer could be a promising approach for its therapeutics. This review examines the roles of the CXCL8-CXCR1/2 signaling axis and how it is implicated in the tumor microenvironment in breast cancer. In addition, we also discuss the potential role of the CXCL8-CXCR1/2 axis in targeted therapeutics for breast cancer.