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Pigment Cell Melanoma Res. 2015 Jan;28(1):105-9. doi: 10.1111/pcmr.12327. Epub 2014 Nov 28.

Riluzole is a radio-sensitizing agent in an in vivo model of brain metastasis derived from GRM1 expressing human melanoma cells.

Author information

1
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.

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.

KEYWORDS:

brain metastasis; glutamate signaling; melanoma

PMID:
25363352
PMCID:
PMC5661976
DOI:
10.1111/pcmr.12327
[Indexed for MEDLINE]
Free PMC Article

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