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Pharmacologic Interventions with NSAIDs

  • Louise R. HoweEmail author
Chapter
  • 1.6k Downloads
Part of the Energy Balance and Cancer book series (EBAC, volume 7)

Abstract

Obesity as a determinant of increased cancer risk and poorer cancer outcome is well established for cancers of several organ sites, including colorectal and postmenopausal breast cancer. Obesity-associated adipose inflammation leads to local and systemic accumulation of inflammatory mediators and hormones, which have multiple proneoplastic effects. Key among these from a pharmacological perspective are cyclooxygenase (COX)-derived prostaglandins (PGs), since COX enzymes are the primary target for nonsteroidal anti-inflammatory drugs (NSAIDs). Overexpression of the inducible PG synthase COX-2 occurs in the majority of colorectal neoplasias and ~40 % of breast cancers and is also evident in inflamed adipose tissue from obese mice and humans. COX/PG signaling has multiple protumorigenic consequences, which provide at least a partial explanation for epidemiologic and experimental observations of reduced cancer risk associated with NSAID use. Notably, COX/PG-mediated upregulation of estrogen biosynthesis and signaling offers a plausible target for NSAID-mediated risk reduction with respect to breast and other hormone-sensitive cancers. Additionally, “off-target” NSAID effects including modulation of NFκB and AMP kinase activity may be of particular significance in the context of obesity. NSAID-mediated amelioration of obesity-­related metabolic dysfunction has been reported, and it seems likely that NSAIDs will be similarly protective for obesity-associated carcinogenesis.

Keywords

Breast Cancer Breast Cancer Risk Colorectal Adenoma Increase Breast Cancer Risk Colorectal Neoplasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Cell and Developmental BiologyWeill Cornell Medical CollegeNew YorkUSA

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