title: RAC1 and melanoma.
abstract: RAC1 is a GTPase member of the RAS superfamily, and RAC1(P29S) was recently identified as the third most common recurrent mutation in melanomas, affecting 4-7% of the patients. This is an oncogenic mutation, because the mutant protein remains mostly in its active GTP-bound form, and its ectopic expression increases the rate of normal melanocytes proliferation and migration. There is limited information regarding the functional role of RAC1(P29S) as a "driver" in human melanogenesis and as a cause for drug resistance. This commentary describes the latest data and provides evidence that supports the notion that RAC1 is activated even in melanoma cells that do not carry the mutation rendering it a good target for therapy. On the other hand, its role in conferring resistance to BRAF or MEK inhibitors is still in question.
authors.affiliation: Yale University School of Medicine, Department of Dermatology, New Haven, Connecticut. Electronic address: ruth.halaban@yale.edu.
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
mesh_terms: D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein
keywords: Hotspot mutation; drug resistance; migration; proliferation