Proinflammatory cytokines in breast cancer: mechanisms of action and potential targets for therapeutics.
Inflammation within the tumor microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. The cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha) and interleukin-1 beta (IL-1beta) are critical mediators of the inflammatory response. Numerous studies have also linked these cytokines to breast cancer progression. As a result, the mechanisms by which these cytokines promote breast cancer have been recently explored using both in vitro and in vivo models. The results from these studies have led to speculation regarding the possible usefulness of targeting these cytokines in breast cancer patients. This review summarizes the most recent studies pertaining to the mechanisms by which proinflammatory cytokines promote breast cancer. Furthermore, the possibilities of targeting these inflammatory mediators in breast cancer patients using inhibitors that are currently being used in the clinic for other inflammatory conditions are discussed. Understanding both the mechanisms by which inflammatory mediators promote breast cancer and the effectiveness of anti-inflammatory drugs in treating breast cancer will lead to novel therapeutic regimens to treat this devastating disease.
Goldberg
Jodi E
JE
Hamline University, Biology Department, 1536 Hewitt Avenue, Saint Paul, MN 55104, USA.
Schwertfeger
Kathryn L
KL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D012307:Risk Factors; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors