*2.7.2 Sulfasalazine (SAS)*

SAS, which is approved for the treatment of rheumatoid arthritis and inflammatory bowel diseases, may be a therapeutic drug for malignant glioma [82]. SAS exerts anti-inflammatory effects by blocking the activation of NF-κB and the Xc antiporter system, which usually causes the uptake of cystine, release of glutamate, and increase in the levels of reactive oxygen species (ROS) [83]. NF-κB is activated in GBM tissues and promotes cell proliferation and survival. SAS blocks

#### **Figure 4.**

*Antitumor mechanisms of acetylsalicylic acid. ASA indicates multimodal effects for glioma cells. ASA suppresses the invasion of glioma cells by activating the expression of connexin 43. ASA also suppresses* c-myc *and* cyclin D1 *through Wnt/β-catenin/TCF pathway and interfered the recovery of DNA damages and adjusted the epithelial-to-mesenchymal transition through SHH/GLI1 pathway. Abbreviation: PGE2, prostaglandin E2.*

### *Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective DOI: http://dx.doi.org/10.5772/intechopen.92803*

the cell cycle and induces apoptosis in vitro and inhibits the growth of brain tumors in mouse xenograft models [83, 84]. However, a phase I/II study of the current therapy with SAS for patients with recurrent malignant glioma showed no clinical benefit of SAS [85]. Recently, a phase I/II study of the current therapy with SAS in patients who were newly diagnosed GBM was performed [86], which showed that there is no increase in OS and PFS in the current therapy with SAS group compared to the current therapy group. Results suggest that this new regimen would improve seizure control; however, the therapeutic effect of SAS would be limited.
