Topical Use of Mammalian Target of Rapamycin (mTOR) Inhibitors in Tuberous Sclerosis Complex—A Comprehensive Review of the Literature

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• 作者：Sergiusz Jó ; źwiak ; MD ; PhD^a ; ^b ; Krzysztof Sadowski ; MD ; PhD^b ; ^{sadowski.ks@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Katarzyna Kotulska ; MD ; PhD^b ; Robert A. Schwartz ; MD ; PhD^c ; ^d ; ^e ; ^f
• 关键词：tuberous sclerosis ; rapamycin ; mTOR inhibitors ; angiofibroma
• 刊名：Pediatric Neurology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：61
• 期：Complete
• 页码：21-27
• 全文大小：788 K

文摘

Tuberous sclerosis complex is a genetically determined multisystem disorder that may affect almost any human organ. The discovery of the mammalian target of rapamycin (mTOR) pathway and its involvement in tuberous sclerosis complex–related pathology has led to the introduction of mTOR inhibitors into clinical practice. Topical administration of mTOR inhibitors for skin lesions related to tuberous sclerosis complex may represent a reasonable alternative for more invasive procedures. A growing number of patients have been described exhibiting positive therapeutic effects from the topical administration of these agents. The aim of this review was to systematically analyze available literature on the use of topical mTOR inhibitors to treat dermatologic lesions related to tuberous sclerosis complex.

Results

A comprehensive review of PubMed, Medscape, and Cochrane databases between 1995 and 2015 was performed to identify available studies describing topical use of mTOR inhibitors in individuals with tuberous sclerosis complex. In most studies, topical mTOR inhibitor application proved to be effective in the treatment of skin lesions related to tuberous sclerosis complex. Facial angiofibromas were the target lesions in most instances. Few studies reported clinical improvement of hypomelanotic macules. These drugs directly address the molecular defect related to tuberous sclerosis complex manifestations.

Conclusions

Currently available clinical data suggest that topical application of mTOR inhibitors may be effective in the treatment of facial angiofibromas associated with tuberous sclerosis complex. Ongoing randomized clinical trials of topical mTOR inhibitors for TSC-related cutaneous lesions should add clarity to the role of these agents.