Molecular mechanisms underlying chronic inflammation-associated cancers

Cancer Lett. 2014 Apr 10;345(2):164-73. doi: 10.1016/j.canlet.2013.08.014. Epub 2013 Aug 26.


Although it is now accepted that chronic inflammation plays an essential role in tumorigenesis, the underlying molecular mechanisms linking inflammation and cancer remain to be fully explored. Inflammatory mediators present in the tumor microenvironment, including cytokines and growth factors, as well as reactive oxygen species (ROS) and reactive nitrogen species (RNS), have been implicated in the etiology of inflammation-associated cancers. Epithelial NADPH oxidase (Nox) family proteins, which generate ROS regulated by cytokines, are upregulated during chronic inflammation and cancer. ROS serve as effector molecules participating in host defense or as chemo-attractants recruiting leukocytes to wounds, thereby influencing the inflammatory reaction in damaged tissues. ROS can alter chromosomal DNA, leading to genomic instability, and may serve as signaling molecules that affect tumor cell proliferation, survival, metabolism, angiogenesis, and metastasis. Targeting Noxs and their downstream signaling components may be a promising approach to pre-empting inflammation-related malignancies.

Keywords: Cancer; Inflammation; NADPH oxidase; Reactive oxygen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Chronic Disease
  • Humans
  • Inflammation / complications*
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • NADPH Oxidases / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Tumor Microenvironment


  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Transcription Factors
  • NADPH Oxidases