title: Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients.
abstract: BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma patients presenting BRAF V600 mutations. This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4-6 weeks during treatment. Eighteen patients with melanoma stages IIIc-IV were enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the tumor markers correlated with tumor burden. MIA and S100 concentrations decreased significantly one month after the beginning of treatment and, upon progression, their concentrations increased significantly above the minimum levels previously achieved. MIA levels lower than 9 μg/L one month after the beginning of treatment and S100 concentrations lower than 0.1 μg/L at the moment of best response were associated with improved progression-free survival. In conclusion, MIA and S100 are useful to monitor response in melanoma patients treated with iBRAF.
authors: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors: Miguel F
authors: MF
authors: Sanmamed
authors: Laboratory of Biochemistry, University Clinic of Navarra, Spain.
authors: Sara
authors: S
authors: Fernández-Landázuri
authors: Laboratory of Biochemistry, University Clinic of Navarra, Spain.
authors: Carmen
authors: C
authors: Rodríguez
authors: Department of Pathology, University Clinic of Navarra, Spain.
authors: María D
authors: MD
authors: Lozano
authors: Department of Pathology, University Clinic of Navarra, Spain.
authors: José I
authors: JI
authors: Echeveste
authors: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors: Jose Luis
authors: JL
authors: Pérez Gracia
authors: Laboratory of Biochemistry, University Clinic of Navarra, Spain.
authors: Estibaliz
authors: E
authors: Alegre
authors: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors: Omar
authors: O
authors: Carranza
authors: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors: Leyre
authors: L
authors: Zubiri
authors: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors: Salvador
authors: S
authors: Martín-Algarra
authors: Laboratory of Biochemistry, University Clinic of Navarra, Spain. Electronic address: agonzaleh@unav.es.
authors: Alvaro
authors: A
authors: González
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D009418:S100 Proteins / Q000097:blood*; D012878:Skin Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D009418:S100 Proteins; D007770:L-Lactate Dehydrogenase; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; BRAF inhibitor; MIA; Melanoma; Melanoma Inhibitory Activity; S100; Therapy; Tumor marker; iBRAF; serine-threonine protein kinase B-RAF