Methods for treating glioma

摘要

The present disclosure provides for method of treatment and/or prevention of disease states that require cystine for maintenance or progression of the disease state. In addition, methods for screening and identifying novel therapeutic agents useful in the treatment of such disease states are described. In one embodiment, the disease state is a cancer, such as, but not limited to, glioma. In this embodiment, methods for the treatment and prevention of glioma by inhibiting cystine uptake or decreasing intracellular cystine concentrations are provided. The present disclosure teaches that glioma cells are dependent on system Xc for cystine uptake. Pharmacological inhibition of system Xc causes a rapid depletion of intracellular glutathione, resulting in decreased cell growth. In contrast, non-malignant astrocytes and cortical neurons remain viable in the presence of Xc inhibitors and continue to take up cystine via alternate amino acid transporters.

主权项

1. A method for treating a glioma, wherein said glioma is dependent on system Xc for uptake of cystine and viability in a subject in need of said treatment, said method comprising administering to said subject a therapeutically effective amount of a N-heterocyclic substituted salicylate compound, where said compound is sulfasalazine, susalimod, disalazine, or salazosulfadimidine, said compound capable of inhibiting cystine uptake by inhibiting system Xc; and administering a radiation therapy.