CXCR4/CXCL12 blockade therapy; a new horizon in TNBC therapy.

The only subtype of breast cancer (BC) without specific therapy is triple-negative breast cancer (TNBC), which represents 15-20% of incidence cases of BC. TNBC encompasses transformed and nonmalignant cells, including cancer-associated fibroblasts (CAF), endothelial vasculature, and tumor-infiltrating cells. These nonmalignant cells, soluble factors (e.g., cytokines), and the extracellular matrix (ECM) form the tumor microenvironment (TME). The TME is made up of these nonmalignant cells, ECM, and soluble components, including cytokines. Direct cell-to-cell contact and soluble substances like cytokines (e.g., chemokines) may facilitate interaction between cancer cells and the surrounding TME. Through growth-promoting cytokines, TME not only enables the development of cancer but also confers therapy resistance. New treatment targets will probably be suggested by comprehending the processes behind tumor development and progression as well as the functions of chemokines in TNBC. In this light, several investigations have shown the pivotal function of the C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis and chemokine receptor type 4 (CXCR4) in the pathophysiology of TNBC. This review provides an overview of the CXCR4/CXCL12 axis' function in TNBC development, metastasis, angiogenesis, and treatment resistance. A synopsis of current literature on targeting the CXCR4/CXCL12 axis for treating and managing TNBC has also been provided.