NF-κB in carcinoma therapy and prevention

Abstract

Background: NF-κB includes a family of signal-activated transcription factors that normally regulate responses to injury and infection but which are aberrantly activated in many carcinomas. Objective: To review the activation and role of NF-κB in pathogenesis and as a target for treatment and prevention in carcinoma. Methods: Evidence from experimental, epidemiological, preclinical studies and clinical trials cited in the literature are reviewed. Results/conclusion: Cumulative evidence implicates NF-κB in cell survival, inflammation, angiogenesis, spread and therapeutic resistance during tumor development, progression and metastasis of carcinomas. Non-specific natural and synthetic agents that inhibit NF-κB have demonstrated activity and safety in prevention or therapy. NF-κB-activating kinases and the proteasome are under investigation for targeted prevention and therapy of carcinoma.

Keywords::

• aspirin
• BMS-345541
• bortezomib
• carcinoma
• CHS-828
• dexamethasone
• inhibitor-kappaB
• MLN-120B
• NF-κB
• NSAIDs
• proteasome
• sulindac

Acknowledgements

The authors would like to thank Shivaani Kummar and James F Battey for reading the manuscript. This research was supported by NIDCD intramural project Z01-DC-00016, NCI-Millennium Pharmaceuticals Cooperative Research and Development Agreement 00676 (CVW), NIH-Pfizer Clinical Research Training Program (MB), and Howard Hughes Medical Institute Research Scholars Program (JC).

Notes