Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

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.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.Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.Tuberous sclerosis complex (TSC) is an autosomal dominant, multi-system tumor disorder characterized by hamartomatous tumors affecting the brain, kidneys, lungs, heart and skin. Clinical manifestations of TSC were recently reviewed [1,2] and major criteria include kidney angiomyolipomas (AMLs), cardiac rhabdomyomas, facial angiofibromas, ungual or periungual fibromas, shagreeen patch, hypomelanotic macule, retinal hamartomas, subependymal nodules, subependymal giant cell astrocytomas (SEGAs), cortical tubers and lymphangioleiomyomatosis (LAM). Although TSC-associated tumors are benign, TSC patients can have a number of medical problems including epilepsy, cognitive impairment, behavior problems, brain lesions (tubers and/or subependymal nodules), skin tumors (facial angiofibromas), cardiac tumors (rhabdomyomas), kidney tumors (AMLs), kidney cysts, renal cell cancer, and pulmonary abnormalities including LAM [3-5]. The skin manifestations of TSC often lead to the diagnosis. Although there are a variety of skin manifestations, the facial angiofibromas in particular cause significant morbidity for patients because they occur on the face and current treatment options are limited [6,7].There are two disease genes: TSC1 on 9q34 and TSC2 on 16p13 [8,9]. Their gene products, hamartin and tuberin respectively, form a tumor suppre