title: An unholy alliance: cooperation between BRAF and NF1 in melanoma development and BRAF inhibitor resistance.
abstract: In this issue of Cancer Discovery, 2 studies provide new evidence implicating loss of the tumor suppressor neurofibromin (NF1) in the biologic behavior of cutaneous melanoma. The first study from Maertens and colleagues describes a new transgenic mouse model in which mutant BRAF cooperates with NF1 loss to drive melanoma development through the abrogation of oncogene-induced senescence. The second, from Whittaker and colleagues, used a high-throughput short hairpin RNA screening approach to identify NF1 loss as a key mediator of acquired and intrinsic BRAF inhibitor resistance. Together these studies provide new insights into the signaling that underlies melanoma initiation and progression and suggests novel therapeutic strategies for patients whose melanomas are BRAF-mutant/NF1-deficient.
authors.affiliation: Departments of 1Cutaneous Oncology and 2Molecular Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Gibney
authors.forename: Keiran S M
authors.initials: KS
authors.lastname: Smalley
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D025542:Neurofibromin 1 / Q000172:deficiency* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D034622:RNA Interference
chemical_list: D025542:Neurofibromin 1; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf