Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective

Abstract

Gliomas are the most common primary brain tumors. Among them, glioblastoma (GBM) possesses the most malignant phenotype. Despite the current standard therapy using an alkylating anticancer agent, temozolomide, most patients with GBM die within 2 years. Novel chemotherapeutic agents are urgently needed to improve the prognosis of GBM. One of the solutions, drug repositioning, which broadens the indications of existing drugs, has gained attention. Herein, we categorize candidate agents, which are newly identified as therapeutic drugs for malignant glioma into 10 classifications based on these original identifications. Some drugs are in clinical trials with hope. Additionally, the obstacles, which should be overcome in order to accomplish drug repositioning as an application for GBM and the future perspectives, have been discussed.

Therapeutic potential of pentamidine for glioma‐initiating cells and glioma cells through multimodal antitumor effects

“…We also undertook an in vivo study by generating a xenograft mouse model of human GBM, and IHC staining of specimens reproduced these findings in the in vitro study. Interestingly, our results indicated that PE has a strong antitumor effect in GICs 16 . Additionally, we successfully generated differentiated GICs and compared the influence of PE on intracellular signaling between GICs and differentiated GICs.…”

“…Interestingly, our results indicated that PE has a strong antitumor effect in GICs. 16 Additionally, we successfully generated differentiated GICs and compared the influence of PE on intracellular signaling between GICs and differentiated GICs.…”

“…These drugs are promptly used for patients because the appropriate usage rules and side‐effects are already known. Previously, we and others identified several compounds that had some therapeutic effects on glioma 9,13–17 . However, none of them have been applied to current clinical treatments 18,19 …”

“…Previously, we and others identified several compounds that had some therapeutic effects on glioma. 9,[13][14][15][16][17] However, none of them have been applied to current clinical treatments. 18,19 Pentamidine, an antiprotozoal drug for pneumonia caused by Pneumocystis jirovecii, suppresses glucose metabolism, amino acid transport, and RNA synthesis.…”

“…Previously, we and others identified several compounds that had some therapeutic effects on glioma. 9 , 13 , 14 , 15 , 16 , 17 However, none of them have been applied to current clinical treatments. 18 , 19 …”