title: Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities.
abstract: The introduction of small molecule BRAF(V600) kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAF(V600) inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAF(V600) inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAF(V600) inhibitors, evoking concern in clinical practice. We review interactions of BRAF(V600) inhibitors and radiation with regard to antitumor effects and an increased radiotoxicity in the healthy tissue.
authors.affiliation: Department of Radiation Oncology & Radiotherapy, University Medical Center Johannes Gutenberg University Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zahnreich
authors.affiliation: Department of Radiation Oncology & Radiotherapy, University Medical Center Johannes Gutenberg University Mainz, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Department of Dermatology, University Medical Center Johannes Gutenberg University Mainz, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Dermatology, University Medical Center Johannes Gutenberg University Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.affiliation: Department of Radiation Oncology & Radiotherapy, University Medical Center Johannes Gutenberg University Mainz, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
mesh_terms: D003131:Combined Modality Therapy / Q000009:adverse effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D011836:Radiation Tolerance / Q000187:drug effects*
chemical_list: D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitor; dabrafenib; melanoma; radiosensitization; radiotherapy; vemurafenib