title: Inflammation, DAMPs, tumor development, and progression: a vicious circle orchestrated by redox signaling.
abstract: CONCLUSIONS
  Increasing evidence indicates that cancer development and progression are promoted by the joint action of redox distress and inflammation, supporting the potential impact of therapies aimed at restoring the redox homeostasis and fighting inflammation.
  
  
  BACKGROUND
  Most of the literature of the last 40 years converges to the view that continuous oxidative stress and chronic inflammation sustain each other, leads to transformation of a normal cell to a neoplastic cell, and promotes tumor progression. Some recent findings, however, support an alternative model whereby the increased production of reactive oxygen species (ROS) is an attempt to defend more than a pathogenetic factor in cancer. Rather, tumor development and progression may be promoted by an excess of antioxidants, induced in both transformed cells and recruited inflammatory cells as an adaptive response to ROS.
  
  
  RESULTS
  Although the link among redox stress, chronic inflammation, and cancer is widely recognized, the underlying mechanisms are far to be understood. The redox unbalance of the microenvironment is likely to modulate the bioactivity of damage-associated molecular pattern molecules such as HMGB1, which are released by stressed tissues and play pleiotropic functions on tumor and inflammatory cells, but how this occur, and the relevant consequences, are still unclear.
  
  
  CONCLUSIONS
  In vivo measurement of cell redox status is an important challenge for future investigations. The improvement of the methodologies for ROS and antioxidant detection will allow a better understanding of the redox-related events in the tumor microenvironment with tremendous application potential in the development of rational combination therapies for cancer treatment.
authors: Cell Biology Unit, IRCSS AOU San Martino-IST , Genoa, Italy .
authors: Patrizia
authors: P
authors: Castellani
authors: Enrica
authors: E
authors: Balza
authors: Anna
authors: A
authors: Rubartelli
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D063646:Carcinogenesis / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species