Role of activated nuclear factor-kappaB in the pathogenesis and therapy of squamous cell carcinoma of the head and neck

Head Neck. 2007 Oct;29(10):959-71. doi: 10.1002/hed.20615.

Abstract

Background: Nuclear factor-kappaB (NF-kappaB), a transcription factor known to modulate expression of factors involved in inflammation, immunity, proliferation, and apoptosis, is constitutively activated and plays a role in pathogenesis and therapeutic resistance in head and neck squamous cell carcinoma (HNSCC). Understanding the molecular alterations leading to aberrant NF-kappaB activation in HNSCC may direct investigators to novel therapeutic targets.

Methods: Results of laboratory and clinical studies are reviewed.

Results: The structure, function, and activation of NF-kappaB, products of NF-kappaB target genes and their role in HNSCC oncogenesis, and current NF-kappaB modulating interventions are described.

Conclusions: Aberrant NF-kappaB activation contributes to the expression of oncogenes and the malignant phenotype observed in HNSCC. NF-kappaB, along with providing a link between cancer and inflammation, may serve as an appropriate therapeutic target to inhibit tumor growth and sensitize cancer cells to established cytotoxic anticancer therapies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Inflammation / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Oncogenes

Substances

  • Antineoplastic Agents
  • NF-kappa B