Although the functions of chemokines in the regulation of immune processes have been studied in some detail, the role of these biomolecules in cancer is not fully understood. Chemokines mediate migration of immune cells and other functions related to immunity. They are also involved in oncogenesis and in tumor progression, invasion, and metastasis through mechanisms similar to their roles in immune functions. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. Consequently, chemokines and their receptors present potential therapeutic targets for anticancer drugs. The chemokine CXCL8, also known as interleukin-8 (IL8), is a proinflammatory molecule that has functions within the tumor microenvironment. Due to its potent angiogenic effects and the activity of the chemokine and its receptors in the promotion of invasion and metastasis, CXCL8 and its receptors are now considered as attractive targets for cancer therapy. This review relates the current understanding of the regulation, signaling, and functions of CXCL8 that contribute to tumor growth and metastasis, and of its role in drug response. 1. Introduction Chemokines, a family of structurally related 8–10？kDa protein molecules, are secreted in diverse tissue environments and are characterized by their involvement in the regulation of hematopoietic cells and inflammatory processes [1, 2]. To date, more than 50 chemokines, which signal through about 20 G-protein-coupled receptors, have been identified [1, 3, 4]. Chemokines are divided into 4 subfamilies (C, CC, CXC, and CX3C), based on their primary structure or function. The structural basis for their classification is the location of the main cysteine residues in their N terminal regions [5–7]. Functionally, chemokines are categorized as “inflammatory” or “homeostatic.” Inflammatory chemokines are released primarily in response to infections; homeostatic chemokines are constitutively secreted at specific sites in the body, such as in the lymphoid organs, where they serve to attract cells that express cognate receptors [8–12]. Although genetic alterations determine the cell of origin of cancer, microenvironmental factors are now known to control the development and progression of the malignant process; hence, these factors are included as a new paradigm in Hallmarks of Cancer [13]. In addition to cancer cells, the tumor microenvironment includes fibroblasts, endothelial cells, macrophages, lymphocytes, neutrophils, and mast cells, all of which respond to various stimuli and communicate through contact and
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