NF-kappaB, inflammation and pancreatic carcinogenesis: NF-kappaB as a chemoprevention target (review).
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.
Zhang
Zhiquan
Z
Department of Medicine, Division of Cancer Prevention, SUNY at Stony Brook, Stony Brook, NY 11794-5200, USA.
Rigas
Basil
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D018890:Chemoprevention; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; C488176:N-acetyl-S-(alpha-methyl-4-(2-methylpropyl)benzeneacetyl)cysteine 4-(nitrooxy)butyl ester; D016328:NF-kappa B; D009566:Nitrates; D001241:Aspirin