4.5 Article

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

Journal

PIGMENT CELL & MELANOMA RESEARCH
Volume 28, Issue 1, Pages -

Publisher

WILEY
DOI: 10.1111/pcmr.12327

Keywords

melanoma; brain metastasis; glutamate signaling

Funding

  1. NCI NIH HHS [R01 CA108720] Funding Source: Medline
  2. NIEHS NIH HHS [R25 ES020721] Funding Source: Medline

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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.

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