title: The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations.
abstract: BRAF V600R-M-D are uncommon mutations, not included in the experimental protocols of BRAF selective inhibitors. We report the evaluation of correlations among different types of BRAF somatic mutations in melanoma and their management with BRAF inhibitors. 21 patients with BRAF mutated metastatic melanoma were enrolled in the protocol with BRAF inhibitors for compassionate use at the University of Modena. Hot spot V600E mutations were found in 19 patients. V600R mutation and double (V600E -V600M) mutation were identified in two melanomas. In one case, V600K mutation was found. Two screening failures were noted. Mean progression free survival at follow-up of to 8 weeks, was 7.6 months. Five patients had a very short follow-up and the experimental protocol is still ongoing, so we cannot provide complete follow-up data. However, all of them are still under treatment and disease progression free. An objective response with few side effects was observed in all patients. in vitro studies with the aim of testing drug sensitivity.
authors: Department of Clinical and Diagnostic Medicine and Public Health, University Hospital of Modena and Reggio Emilia, Modena, Italy. giovanni.ponti@unimore.it
authors: Giovanni
authors: G
authors: Ponti
authors: Giovanni
authors: G
authors: Pellacani
authors: Aldo
authors: A
authors: Tomasi
authors: Fabio
authors: F
authors: Gelsomino
authors: Andrea
authors: A
authors: Spallanzani
authors: Roberta
authors: R
authors: Depenni
authors: Samer
authors: S
authors: Al Jalbout
authors: Lisa
authors: L
authors: Simi
authors: Lorella
authors: L
authors: Garagnani
authors: Stefania
authors: S
authors: Borsari
authors: Andrea
authors: A
authors: Conti
authors: Cristel
authors: C
authors: Ruini
authors: Annalisa
authors: A
authors: Fontana
authors: Gabriele
authors: G
authors: Luppi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D057176:Compassionate Use Trials; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009367:Neoplasm Staging; D010091:Oximes / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib