Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model.
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.
Rauktys
Aubrey
A
Translational Medicine Division, Department of Medicine, Brigham & Women's Hospital, One Blackfan Circle, Karp Research Building, Boston, MA, 02115 USA. arauktys21@gmail.com
Lee
Nancy
N
Lee
Laifong
L
Dabora
Sandra L
SL
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
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus