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Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology

机译:雷帕霉素(mTOR)抑制剂在哺乳动物皮肤病学中的治疗用途的研究进展

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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.
机译:在使用哺乳动物雷帕霉素靶标(mTOR)抑制剂(mTORIs)作为免疫抑制剂和抗增殖剂方面取得了重大进展。在了解mTOR信号通路及其对肿瘤发生和血管增殖的下游影响方面的最新进展,已拓宽了mTORI在许多具有挑战性的疾病中的临床应用,例如结节性硬化症,先天性肺炎,复杂的血管异常和炎症性皮肤病。全身性mTORI治疗在这些领域已显示出益处,但伴随着明显的副作用,有时需要放假。为减轻全身性mTORIs在皮肤病学应用中的副作用,已开展了初步工作来评估经皮治疗的潜力,并且证据表明,经皮递送mTORIs可以有效地长期治疗,同时避免全身毒性。需要其他大型安慰剂对照,双盲,随机研究来评估局部治疗的有效性,安全性,持续时间和耐受性。这篇综述的目的是提供有关mTORI在许多皮肤疾病管理中的新用途的最新信息。

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