Enzyme inhibition may brighten glioma treatment outlook

Medications were able to block a newly identified cancer-promoting pathway and delay glioma growth in mice, suggesting a new treatment option to combat malignant glioma—an aggressive brain tumor associated with a poor prognosis.

With the best available treatments, median survival for patients with the most severe, aggressive form of malignant glioma (grade IV glioma, or glioblastoma multiforme) is 9 to 15 months. However, new therapeutic options may be developed now that a team of researchers from the Cleveland Clinic, Ohio, has defined a novel molecular pathway that cancer stem cells use to promote tumor growth.

As Jeremy N. Rich, MD, and colleagues have demonstrated that glioma stem cells (GSCs) produce nitric oxide through increased levels of the enzyme nitric oxide synthase 2 (NOS2) (Cell. 2011;146[1]:53-66). Unlike non-GSCs and normal neural stem cells, GSCs depend on NOS2 activity for growth; decreasing the level or the activity of this enzyme can reduce GSC growth. When the investigators gave NOS2-inhibiting drugs to mice with gliomas, the growth of the tumors was delayed.

Rich's team also learned that increased levels of NOS2 are linked with decreased survival in persons with glioma.

“These data provide insight into how GSCs are mechanistically distinct from their less tumorigenic counterparts and suggest that NOS2 inhibition may be an efficacious approach to treating this devastating disease," concluded the investigators.

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