Pilot study for the treatment of cutaneous neurofibromas in neurofibromatosis type 1 patients using topical sirolimus gel

To the Editor: Neurofibromatosis type 1 (NF1) is a genetic disorder involving plexiform and cutaneous neurofibromas (cNFs) in which the constitutive activation of MAPK (mitogen-activated protein kinase) and mechanistic target of rapamycin complex 1 (mTORC1) promote tumorigenesis. 1 Bergoug M. Doudeau M. Godin F. Mosrin C. Vallée B. Bénédetti H. Neurofibromin structure, functions and regulation. Cells. 2020; 9 Crossref PubMed Scopus (55) Google Scholar Unlike the case for plexiform neurofibromas, 2 Dombi E. Baldwin A. Marcus L.J. et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med. 2016; 375: 2550-2560 Crossref PubMed Scopus (429) Google Scholar no clinical trials have been conducted on cNFs that impair quality of life. mTORC1 is involved in the tumor microenvironment in addition to cell proliferation. Therefore, mTORC1 inhibitors appear extremely effective against NF1 tumors, where the microenvironment is essential for tumorigenesis. 3 Zhu Y. Ghosh P. Charnay P. Burns D.K. Parada L.F. Neurofibromas in NF1: schwann cell origin and role of tumor environment. Science. 2002; 296: 920-922 Crossref PubMed Scopus (512) Google Scholar cNFs strictly localize to the dermis. To determine sirolimus gel efficacy and safety, a randomized, double-blind, placebo-controlled, pilot study was performed between March 16, 2016 and January 11, 2017. The trial examined 0.2% and 0.4% sirolimus gel, which delivered high concentrations of sirolimus to the dermis via topical application. 4 Kitayama K. Maeda S. Nakamura A. Katayama I. Wataya-Kaneda M. Efficiency of sirolimus delivery to the skin is dependent on administration route and formulation. J Dermatol Sci. 2019; 94: 350-353 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar