Role of activated nuclear factor-kappaB in the pathogenesis and therapy of squamous cell carcinoma of the head and neck.
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.
Allen
Clint T
CT
Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 10 Center Drive, CRC 4-2732, Bethesda, Maryland 20892, USA.
Ricker
Justin L
JL
Chen
Zhong
Z
Van Waes
Carter
C
D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D009857:Oncogenes
D000970:Antineoplastic Agents; D016328:NF-kappa B