Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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ATM-NF-κB Connection as a Target for Tumor Radiosensitization

Author(s): Kazi Mokim Ahmed, Jian Jian Li.

Abstract:

Ionizing radiation (IR) plays a key role in both areas of carcinogenesis and anticancer radiotherapy. The ATM (ataxia-telangiectasia mutated) protein, a sensor to IR and other DNA-damaging agents, activates a wide variety of effectors involved in multiple signaling pathways, cell cycle checkpoints, DNA repair and apoptosis. Accumulated evidence also indicates that the transcription factor NF-κB (nuclear factor-kappaB) plays a critical role in cellular protection against a variety of genotoxic agents including IR, and inhibition of NF-κB leads to radiosensitization in radioresistant cancer cells. NF-κB was found to be defective in cells from patients with A-T (ataxia-telangiectasia) who are highly sensitive to DNA damage induced by IR and UV lights. Cells derived from A-T individuals are hypersensitive to killing by IR. Both ATM and NF-κB deficiencies result in increased sensitivity to DNA double strand breaks. Therefore, identification of the molecular linkage between the kinase ATM and NF-κB signaling in tumor response to therapeutic IR will lead to a better understanding of cellular response to IR, and will promise novel molecular targets for therapy-associated tumor resistance. This review article focuses on recent findings related to the relationship between ATM and NF-κB in response to IR. Also, the association of ATM with the NF-κB subunit p65 in adaptive radiation response, recently observed in our lab, is also discussed.

Keywords: ATM, NF-κB, ionizing radiation

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Article Details

VOLUME: 7
ISSUE: 4
Year: 2007
Page: [335 - 342]
Pages: 8
DOI: 10.2174/156800907780809769
Price: $58