Ku70 acetylation in neuroblastoma pathogenesis and therapy.
Neuroblastoma is a cancer that occurs in children. It develops from stem cells that normally give rise to parts of the peripheral nervous system and adrenal glands. Although most children with localized neuroblastoma are cured, children with wide-spread disease have a small chance of survival even after surgery, chemotherapy, radiation and bone marrow transplantation. Ten to fifteen percent of patients die from treatment complications, and long-term survival is less than 30%. Although contemporary molecular tumor marker discoveries have improved prognostication, few have led to new therapeutic approaches. To solve this problem, we are working to understand which molecules in the stem cells from which this cancer arises malfunction to cause neuroblastoma and apply this information to develop new models to treat this disease. Our efforts have focused on the functional regulation of a protein called Ku70, which coordinately regulates DNA repair and cell death. We propose that the incorrect balance between these two activities underlies this cancer's development, and that re-balancing with drug therapy offers a way to treat this disease.
Castle
Valerie
V
University of Michigan, Department of Pediatrics and Communicable Diseases, 1500 East Medical Center Drive, Room D3202 MPB, Ann Arbor, MI 48109-5718, USA. vcastle@umich.edu
Kwok
Roland
R
Opipari
Anthony
A
Subramanian
Chitra
C
D000107:Acetylation; D034961:Antigens, Nuclear / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002648:Child; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D000072200:Ku Autoantigen; D008954:Models, Biological; D009447:Neuroblastoma / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D034961:Antigens, Nuclear; C494826:BAX protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D051028:bcl-2-Associated X Protein; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen