NF-kappa B-mediated adaptive resistance to ionizing radiation.
Ionizing radiation (IR) began to be a powerful medical modality soon after Wilhelm Röntgen's discovery of X-rays in 1895. Today, more than 50% of cancer patients receive radiotherapy at some time during the course of their disease. Recent technical developments have significantly increased the precision of dose delivery to the target tumor, making radiotherapy more efficient in cancer treatment. However, tumor cells have been shown to acquire a radioresistance that has been linked to increased recurrence and failure in many patients. The exact mechanisms by which tumor cells develop an adaptive resistance to therapeutic fractional irradiation are unknown, although low-dose IR has been well defined for radioadaptive protection of normal cells. This review will address the radioadaptive response, emphasizing recent studies of molecular-level reactions. A prosurvival signaling network initiated by the transcription factor NF-kappa B, DNA-damage sensor ATM, oncoprotein HER-2, cell cyclin elements (cyclin B1), and mitochondrial functions in radioadaptive resistance is discussed. Further elucidation of the key elements in this prosurvival network may generate novel targets for resensitizing the radioresistant tumor cells.
Ahmed
Kazi Mokim
KM
Division of Molecular Radiobiology and Graduate Program of Radiation and Cancer Biology, Purdue University School of Health Sciences, West Lafayette, IN 47907, USA.
Li
Jian Jian
JJ
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D018734:Genes, erbB-2 / Q000528:radiation effects; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics / Q000276:immunology; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000528:radiation effects*
D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species