Modulation of antiapoptotic cell signaling pathways in non-small cell lung cancer: the role of NF-kappaB

Seminars in Thoracic and Cardiovascular Surgery
Chadrick E DenlingerDavid R Jones

Abstract

Apoptosis, or programmed cell death, is a natural phenomenon that is critical for normal embryonic development and the maintenance of homeostasis in multicellular organisms. In adults, apoptosis represents a protective strategy that limits the spread of infection and helps prevent the development of malignancies. Cells acquiring nonrepairable DNA mutations are capable of "committing suicide" to prevent propagation of acquired genetic mutations and to eliminate their own malignant potential. Although malignant cells maintain the necessary intracellular apoptotic machinery, inappropriate inhibition of apoptosis allows for continued tumor growth and metastases. The majority of nonsmall cell lung cancer (NSCLC) exhibits dysregulated antiapoptotic pathways involving the transcription factor NF-kappaB. In addition, in NSCLC both chemotherapy and radiation upregulate antiapoptotic and cell-cycle regulatory proteins through NF-kappaB-dependent signaling mechanisms. Preclinical and phase I clinical trials suggest that inhibition of NF-kappaB markedly attenuates the resistance of NSCLC to undergo apoptosis and sensitizes these cells to chemotherapy. Modulation of the antiapoptotic cascade mediated by NF-kappaB, combined with either tradi...Continue Reading

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Citations

Feb 12, 2008·Journal of Cancer Research and Clinical Oncology·Katerina VrzalikovaZdenek Kolar
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Jan 5, 2011·Frontiers in Bioscience (Landmark Edition)·Wenshu ChenYong Lin
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Jun 27, 2006·The Annals of Thoracic Surgery·Zhenfa ZhangChangli Wang
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