title: Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model.
abstract: BACKGROUND
  Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.
  
  
  METHODS
  0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.
  
  
  RESULTS
  Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.
  
  
  CONCLUSIONS
  Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
authors.affiliation: Translational Medicine Division, Department of Medicine, Brigham & Women's Hospital, One Blackfan Circle, Karp Research Building, Boston, MA, 02115 USA. arauktys21@gmail.com
authors.forename: Aubrey
authors.initials: A
authors.lastname: Rauktys
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee
authors.forename: Laifong
authors.initials: L
authors.lastname: Lee
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Dabora
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011494:Protein Kinases / Q000187:drug effects*; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012869:Skin Absorption; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus