title: Searching for the Chokehold of NRAS Mutant Melanoma.
abstract: Up to 18% of melanomas harbor mutations in the neuroblastoma rat-sarcoma homolog (NRAS). Yet, decades of research aimed to interfere with oncogenic RAS signaling have been largely disappointing and have not resulted in meaningful clinical outputs. Recent advances in disease modeling, structural biology, and an improved understanding of RAS cycling as well as RAS signaling networks have renewed hope for developing strategies to selectively block hyperactive RAS function. This review discusses direct and indirect blocking of activated RAS with a focus on current and potential future therapeutic approaches for NRAS mutant melanoma.
authors.affiliation: Department of Dermatology, Mt. Zion Cancer Research Center, University of California San Francisco, San Francisco, California, USA; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria. Electronic address: cposch81@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Posch
authors.affiliation: Department of Dermatology, Mt. Zion Cancer Research Center, University of California San Francisco, San Francisco, California, USA; Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Vujic
authors.affiliation: Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Babak
authors.initials: B
authors.lastname: Monshi
authors.affiliation: Department of Dermatology, Mt. Zion Cancer Research Center, University of California San Francisco, San Francisco, California, USA; Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Sanlorenzo
authors.affiliation: Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Weihsengruber
authors.affiliation: Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
authors.forename: Klemens
authors.initials: K
authors.lastname: Rappersberger
authors.affiliation: Department of Dermatology, Mt. Zion Cancer Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Ortiz-Urda
mesh_terms: D000495:Allosteric Site; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004359:Drug Therapy, Combination / Q000379:methods; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D007107:Immune System; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; D050505:Mutant Proteins; D034741:RNA, Small Interfering; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D018631:ras Proteins