title: Chemokines as therapeutic targets in non-small cell lung cancer.
abstract: Angiogenesis, defined as the generation of new blood vessels from pre-existing vessels, is one of life's essential processes. Inflammation and angiogenesis, while distinct and separable, are closely related processes. One of the hallmarks of chronic inflammation is granulation tissue, a prominent feature of which is neovascularization. Whenever tissue constituents proliferate, repair, or hypertrophy, such change must be accompanied by a proportional increase in capillary blood supply to assure delivery of nutrients, and removal of metabolic waste. This absolute dependence suggests two characteristics of angiogenesis. First, under normal conditions the process must be tightly controlled. Second, in the absence of such strict control, abnormal physiology, or disease is likely to result. The role of angiogenesis in solid tumor growth has attracted a great deal of attention as a potential therapeutic target. Lung cancer is a particularly devastating disease in industrialized countries. The majority of patients with lung cancer are faced with very poor therapeutic options, and gaining insight to the mechanism of angiogenesis in this disease has obvious implications for the design of therapeutic agents. Research in our laboratories has demonstrated that chemokines (chemotactic cytokines) are pivotal determinants of the angiogenic activity of non-small cell lung cancer (NSCLC). This review will focus on the evidence supporting the central role of these molecules in lung cancer angiogenesis, and focus on potential novel means of targeting this family of angiogenic regulators.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: White
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: D A
authors.initials: DA
authors.lastname: Arenberg
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D002455:Cell Division / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018925:Chemokines