Chemokines in bone-metastatic breast cancer: Therapeutic opportunities.

Due to non-response to chemotherapy, incomplete surgical resection, and resistance to checkpoint inhibitors, breast cancer with bone metastasis is notoriously difficult to cure. Therefore, the development of novel, efficient strategies to tackle bone metastasis of breast cancer is urgently needed. Chemokines, which induce directed migration of immune cells and act as guide molecules between diverse cells and tissues, are small proteins indispensable in immunity. These complex chemokine networks play pro-tumor roles or anti-tumor roles when produced by breast cancer cells in the tumor microenvironment. Additionally, chemokines have diverse roles when secreted by various immune cells in the tumor microenvironment of breast cancer, which can be roughly divided into immunosuppressive effects and immunostimulatory effects. Recently, targeting chemokine networks has been shown to have potential for use in treatment of metastatic malignancies, including bone-metastatic breast cancer. In this review, we focus on the role of chemokines networks in the biology of breast cancer and metastasis to the bone. We also discuss the therapeutic opportunities and future prospects of targeting chemokine networks, in combination with other current standard therapies, for the treatment of bone-metastatic breast cancer.