title: IGF-I receptor inhibition combined with rapamycin or temsirolimus inhibits neuroblastoma cell growth.
abstract: BACKGROUND
  Neuroblastoma is the third most common solid tumor in children. Treatment continues to be challenging. The pathogenesis of neuroblastoma has been related to expression of the type 1 insulin-like growth factor receptor (IGF1R) and to transcription factor MYC-N amplification. Previous studies have shown that MYC-N expression is disrupted by blockade of the IGF1R with a specific monoclonal antibody, alphaIR3. Inhibition of IGF1R signaling can be accomplished by other agents, including rapamycin or temsirolimus, which target mTOR (mammalian target of rapamycin).
  
  
  METHODS
  BE-2(c) and IMR-32 neuroblastoma cell lines were treated with varying concentrations of alphaIR3, rapamycin and temsirolimus alone or in combination and the viable cells were counted.
  
  
  RESULTS
  Blockade of IGF1R signaling significantly inhibited cell growth as compared to untreated controls (p < 0.05), and a combination of agents was more effective than each agent alone.
  
  
  CONCLUSIONS
  The combination of rapamycin or temsirolimus with alphaIR3 blocks the IGF1R signaling pathway and has an antiproliferative effect on neuroblastoma cells warranting further investigations using inhibitors of IGF1R signaling as novel combination therapy for neuroblastoma.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7220, USA. dcoulter@unch.unc.edu
authors.forename: Don W
authors.initials: DW
authors.lastname: Coulter
authors.forename: Julie
authors.initials: J
authors.lastname: Blatt
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: D'Ercole
authors.forename: Billie M
authors.initials: BM
authors.lastname: Moats-Staats
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
chemical_list: C401859:temsirolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus