pitavastatin has been researched along with Glioblastoma* in 1 studies
1 other study(ies) available for pitavastatin and Glioblastoma
| Article | Year |
|---|---|
Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs.
Glioblastoma (GBM) is a therapeutic challenge, associated with high mortality. More effective GBM therapeutic options are urgently needed. Hence, we screened a large multi-class drug panel comprising the NIH clinical collection (NCC) that includes 446 FDA-approved drugs, with the goal of identifying new GBM therapeutics for rapid entry into clinical trials for GBM.. Screens using human GBM cell lines revealed 22 drugs with potent anti-GBM activity, including serotonergic blockers, cholesterol-lowering agents (statins), antineoplastics, anti-infective, anti-inflammatories, and hormonal modulators. We tested the 8 most potent drugs using patient-derived GBM cancer stem cell-like lines. Notably, the statins were active in vitro; they inhibited GBM cell proliferation and induced cellular autophagy. Moreover, the statins enhanced, by 40-70 fold, the pro-apoptotic activity of irinotecan, a topoisomerase 1 inhibitor currently used to treat a variety of cancers including GBM. Our data suggest that the mechanism of action of statins was prevention of multi-drug resistance protein MDR-1 glycosylation. This drug combination was synergistic in inhibiting tumor growth in vivo. Compared to animals treated with high dose irinotecan, the drug combination showed significantly less toxicity.. Our data identifies a novel combination from among FDA-approved drugs. In addition, this combination is safer and well tolerated compared to single agent irinotecan.. Our study newly identifies several FDA-approved compounds that may potentially be useful in GBM treatment. Our findings provide the basis for the rational combination of statins and topoisomerase inhibitors in GBM. Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Autophagy; Blood-Brain Barrier; Brain Neoplasms; Camptothecin; Cell Line, Tumor; Cell Survival; Disease-Free Survival; Dose-Response Relationship, Drug; Down-Regulation; Drug Approval; Drug Synergism; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Irinotecan; Mice; Mice, Nude; Neoplastic Stem Cells; Quinolines; Spheroids, Cellular; United States; United States Food and Drug Administration; Xenograft Model Antitumor Assays | 2014 |