title: Riluzole is a radio-sensitizing agent in an in vivo model of brain metastasis derived from GRM1 expressing human melanoma cells.
abstract: Approximately 50% of patients having metastatic melanoma develop brain metastases during the course of their illness. Evidence exists that melanoma cells have increased aptitude for the repair of sublethal DNA damage caused by ionizing radiation therapy. To address the radio-resistance of melanoma, many groups adopted radiotherapy schedules that deliver larger daily fractions of radiation, but due to the risk of neurotoxicity, these large fractions cannot be delivered to the whole brain for patients with brain metastases. Here, we used orthotopic implanted GRM1 expressing human melanoma cell xenografts in mice, to demonstrate that animals receiving concurrent glutamate signaling blockade (riluzole) and radiation led to a decrease in intracranial tumor growth compared to either modality alone. These preclinical results suggest riluzole may cause radio-sensitization that offers enhanced efficacy for a subset of human melanoma patients undergoing radiotherapy for brain metastasis.
authors.affiliation: Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University, Piscataway, NJ, USA; Joint Graduate Program of Toxicology and Pharmacology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Wall
authors.forename: Lumeng J
authors.initials: LJ
authors.lastname: Yu
authors.forename: Atif
authors.initials: A
authors.lastname: Khan
authors.forename: Bruce
authors.initials: B
authors.lastname: Haffty
authors.forename: James S
authors.initials: JS
authors.lastname: Goydos
authors.forename: Suzie
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary*; D045744:Cell Line, Tumor; D002999:Clone Cells; D004195:Disease Models, Animal; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D049449:Luminescence; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D011838:Radiation-Sensitizing Agents; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D019782:Riluzole; D008156:Luciferases
keywords: brain metastasis; glutamate signaling; melanoma