NF-kappaB, inflammation and pancreatic carcinogenesis: NF-kappaB as a chemoprevention target (review)

Int J Oncol. 2006 Jul;29(1):185-92.

Abstract

Pancreatic cancer is the most deadly of all gastrointestinal malignancies with near zero five-year survival. This review summarizes our understanding of the potentially important role of inflammation in cancer in general and pancreatic cancer in particular. Nuclear factor kappaB (NF-kappaB), a mediator of inflammatory responses, plays a significant role in carcinogenesis and is now emerging as a link between inflammation and cancer. NF-kappaB is activated in over two thirds of human pancreatic cancers; participates in early events of pancreatic carcinogenesis through its interactions with signaling pathways; and suppression of its activation restores pancreatic cell kinetics, mainly normalizing the suppressed apoptosis of pancreatic cancer. NF-kappaB is an excellent target for chemoprevention and its modulation for pancreatic cancer prevention appears promising. The next few years will likely expand our understanding of NF-kappaB biology; solidify NF-kappaB's role as a major link between chronic inflammation and pancreatic carcinogenesis; and witness the development of NF-kappaB-based approaches to pancreatic cancer prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Aspirin / analogs & derivatives
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Chemoprevention
  • Humans
  • Inflammation / metabolism*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nitrates / pharmacology
  • Nitrates / therapeutic use
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / prevention & control

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • N-acetyl-S-(alpha-methyl-4-(2-methylpropyl)benzeneacetyl)cysteine 4-(nitrooxy)butyl ester
  • NF-kappa B
  • Nitrates
  • Aspirin