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Anti-inflammatory shows promise in brain tumor treatment

Posted on: 06/24/2007

Published in UAB Insight, Winter 2006

Anti-inflammatory shows promise in brain tumor treatment

UAB researchers have discovered that sulfasalazine (Azulfidine), used for decades to treat chronic inflammatory conditions such as Crohn disease and rheumatoid arthritis, may also stop or reverse growth of the dreaded glioblastoma multiforme — arguably one of the most deadly human cancers. UUntil now, these tumors were essentially impossible to treat, with a median survival rate of 1 year.

Led by UAB neurobiologist and Civitan International Research Center Director Harald W. Sontheimer, PhD, UAB researchers found in animal studies that sulfasalazine inhibits the transport protein that allows glioma cells to produce glutathione, an antioxidant that protects cancer cells from oxygen-free radicals. Findings were published August 2005 in The Journal of Neuroscience (2[31]:7101-7110). “Without glia, the brain would not function,� says Sontheimer of the normal glial cells that have been his study focus for 20 years. Scientists do not know what catalyzes a neoplastic proliferation of glia and formation of gliomas within the enclosed space of the brain. “The main difference between these brain tumor cells and normal cells is they have only one supply line for cystine to produce glutathione,� says Sontheimer. “We put one and one together and essentially showed in gliomas that sulfasalazine is acting on the cystine transporter and thereby depleting glutathione. It was a serendipitous discovery to find the drug effectively inhibits that transporter.�

Study for Late-stage Cancer

On the basis of these findings in animal studies, Sontheimer and principal investigator and UAB neuro-oncologist Burt Nabors, MD, designed a pilot study to determine “central nervous system availability and activity of sulfasalazine in patients with recurrent malignant glioma.� Eligible are late-stage glioblastoma patients who have exhausted standard-of-care options (radiation, chemotherapy, and debulking surgery) and are also candidates for craniotomy to debulk a portion of the tumor. Exclusion criteria include allergies to sulfur-containing drugs, pregnancy, and breastfeeding.

“The only conclusively demonstrated risk factor for glioblastoma is prior head and neck radiation, which increases fourfold the risk of tumor development,� says Nabors, who will collect tumor tissue and cerebrospinal fluid to measure levels of sulfasalazine and its metabolites.

“Based on our understanding of underlying biology, we feel confident this drug will have a therapeutic effect in patients,� Sontheimer says of sulfasalazine, which is approved for humans with inflammatory diseases and has been used for more than 50 years in clinical settings. The Food and Drug Administration is allowing off-label application for the clinical study.

Sontheimer remains cautiously optimistic about possibilities for sulfasalazine both as a treatment for glioblastomas, as well as an enhancement of radiation and chemotherapeutics for other multidrug-resistant cancers. “The hopeful outcome is that we have a readily available drug with a good safety profile for oral delivery that can quickly be used in patients with this devastating disease.�

For more information
Dr. Harald Sontheimer
Dr. Burt Nabors

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