title: Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology.
abstract: Significant developments in the use of mammalian target of rapamycin (mTOR) inhibitors (mTORIs) as immunosuppressant and antiproliferative agents have been made. Recent advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTORIs in many challenging disorders such as tuberous sclerosis complex, pachyonychia congenita, complex vascular anomalies, and inflammatory dermatoses. Systemic mTORI therapy has shown benefits in these areas, but is associated with significant side effects that sometimes necessitate drug holidays. To mitigate the side effects of systemic mTORIs for dermatologic applications, preliminary work to assess the potential of percutaneous therapy has been performed, and the evidence suggests that percutaneous delivery of mTORIs may allow for effective long-term therapy while avoiding systemic toxicities. Additional large placebo-controlled, double-blinded, randomized studies are needed to assess the efficacy, safety, duration, and tolerability of topical treatments. The objective of this review is to provide updated information on the novel use of mTORIs in the management of many cutaneous disorders.
authors.affiliation: Stanford University School of Medicine, Palo Alto, California.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Fogel
authors.affiliation: Cambridge Mansions, London, United Kingdom.
authors.forename: Sharleen
authors.initials: S
authors.lastname: Hill
authors.affiliation: Dermatology, Stanford University School of Medicine, Palo Alto, California; Pediatrics, Stanford University School of Medicine, Palo Alto, California; Pediatric Dermatology, Stanford University School of Medicine, Palo Alto, California; Stanford University School of Medicine, Palo Alto, California. Electronic address: jteng3@stanford.edu.
authors.forename: Joyce M C
authors.initials: JM
authors.lastname: Teng
mesh_terms: D006801:Humans; D007166:Immunosuppressive Agents; D012871:Skin Diseases / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014402:Tuberous Sclerosis / Q000188:drug therapy
chemical_list: D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: antiproliferative; autoimmune; drug repurposing; genodermatosis; immunosuppression; inflammatory; mammalian target of rapamycin; neoplasia; percutaneous therapy; rapamycin; sirolimus; vascular anomalies