Topical rapamycin (sirolimus) for facial angiofibromas

Abstract

Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Rapamycin is a novel class of anticancer and immunosuppressant drugs targeting the proteins at molecular level. Rapamycin (sirolimus) is routinely incorporated in drug-eluting stents used for cardiac angioplasty. In recent years, rapamycin was found to be efficacious in managing the symptom complex of tuberous sclerosis, i.e. renal angiomyolipoma, giant cell astrocytoma and pulmonary lymphangiomyomatosis. Various investigators have also proved that topically applied rapamycin causes regression of facial angiofibromas, giving better cosmetic results.

Keywords: Facial angiofibromas; Mechanism of action; Rapamycin; Tuberous sclerosis.

Figure 1

Mechanism of action of rapamycin: Intracellularly rapamycin binds to FKBP12 protein and binds to mTORC1 thereby inhibiting its downstream pathway. Protein products of TSC 1 and TSC 2 gene i.e. hamartin and tuberin inhibits the functioning of mTORC1 pathway via Rheb protein and thus mutation of these TSC proteins causes constitutive activation of mTOR pathway leading to cellular proliferation