RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights

Steven D Rhodes; Frank McCormick; Ross L Cagan; Annette Bakker; Verena Staedtke; Ina Ly; Matthew R Steensma; Sang Y Lee; Carlos G Romo; Jaishri O Blakeley; Kavita Y Sarin

doi:10.1016/j.jid.2023.01.043

RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights

J Invest Dermatol. 2023 Aug;143(8):1358-1368. doi: 10.1016/j.jid.2023.01.043. Epub 2023 May 27.

Authors

Affiliations

¹ Division of Hematology-Oncology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA; Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA; Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
³ School of Cancer Sciences, University of Glasgow, Glasgow, Scotland.
⁴ Children's Tumor Foundation, New York, New York, USA.
⁵ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶ Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁷ Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA; Helen DeVos Children's Hospital, Spectrum Health System, Grand Rapids, Michigan, USA; College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA.
⁸ Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA. Electronic address: ksarin@stanford.edu.

Abstract

Cutaneous neurofibromas (cNFs) are the most common tumor in people with the rasopathy neurofibromatosis type 1. They number in hundreds or even thousands throughout the body, and currently, there are no effective interventions to prevent or treat these skin tumors. To facilitate the identification of novel and effective therapies, essential studies including a more refined understanding of cNF biology and the role of RAS signaling and downstream effector pathways responsible for cNF initiation, growth, and maintenance are needed. This review highlights the current state of knowledge of RAS signaling in cNF pathogenesis and therapeutic development for cNF treatment.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neurofibroma* / metabolism
Neurofibroma* / pathology
Neurofibromatosis 1* / genetics
Signal Transduction
Skin Neoplasms* / genetics
Skin Neoplasms* / metabolism

Grants and funding

R35 CA197709/CA/NCI NIH HHS/United States