The current management of brain metastasis in melanoma: a focus on riluzole.

Brain metastasis is a common endpoint in human malignant melanoma, and the prognosis for patients remains poor despite advancements in therapy. Current treatment for melanoma metastatic to the brain is grouped into those providing symptomatic relief such as corticosteroids and antiepileptic agents, to those that are disease modifying. Related to the latter group, recent studies have demonstrated that aberrant glutamate signaling plays a role in the transformation and maintenance of various cancer types, including melanoma. Glutamate secretion from these and surrounding cells have been found to stimulate regulatory pathways that control tumor growth, proliferation and survival in vitro and in vivo. The antiglutamatergic actions of an inhibitor of glutamate release, riluzole, have been detected by its ability to clear glutamate from the synapse, and it has been shown to inhibit glutamate release rather than directly inhibiting glutamate receptors. Preclinical studies have demonstrated the ability of riluzol...