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Repurposed Drugs

Drug repurposing investigates whether medicines already used for other conditions could also target glioblastoma biology or improve treatment tolerance. Although existing safety information can accelerate development, most repurposed approaches remain supported by laboratory, retrospective or early-phase clinical evidence and should not be considered established glioblastoma treatments.

Highlighted Papers

Halatsch et al., 2021 — “A Phase Ib/IIa Trial of 9 Repurposed Drugs Combined with Temozolomide for the Treatment of Recurrent Glioblastoma: CUSP9v3”

CUSP9v3 combines nine repurposed medicines with temozolomide to target several tumour-survival pathways simultaneously. The regimen could be administered to ten patients under careful monitoring, but the small uncontrolled study could not establish treatment efficacy.

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Gallia et al., 2020 — “Mebendazole and Temozolomide in Patients with Newly Diagnosed High-Grade Gliomas: Results of a Phase 1 Clinical Trial”

This phase I trial investigated the antiparasitic medicine mebendazole alongside temozolomide. High-dose mebendazole demonstrated acceptable long-term safety, but the study was not designed to establish a survival benefit.

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Lee et al., 2024 — “High-Throughput Identification of Repurposable Neuroactive Drugs with Potent Anti-Glioblastoma Activity”

A large-scale drug screen identified the antidepressant vortioxetine as a potential anti-glioblastoma treatment. Activity was demonstrated in laboratory and animal models, but clinical benefit in patients has not yet been established.

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Bernstock et al., 2025 — “Gabapentinoids Confer Survival Benefit in Human Glioblastoma”

This multi-institutional retrospective study associated postoperative gabapentin use with longer survival in patients with newly diagnosed glioblastoma. The findings provide a rationale for prospective trials but do not prove that gabapentin itself caused the survival difference.

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Yoon et al., 2023 — “Efficacy and Safety of Metformin Plus Low-Dose Temozolomide in Patients with Recurrent or Refractory Glioblastoma: A Randomized, Prospective, Multicenter, Double-Blind, Controlled, Phase 2 Trial (KNOG-1501 Study)”

This randomised trial compared metformin plus low-dose temozolomide with temozolomide and placebo in 81 patients. The combination was tolerable but did not significantly improve progression-free or overall survival.

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Further Literature

  • Alrosan, A. Z., Heilat, G. B., Al Subeh, Z. Y. et al. (2023): The effects of statin therapy on brain tumors, particularly glioma: a review. Anticancer Drugs. 2023 Oct 1;34(9):985-994. https://doi.org/10.1097/CAD.0000000000001533

  • Altwairgi, A., Alnajjar, F. Alhussain, H. et al. (2019): Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma (ART): Final analysis report. Annals of Oncology, Volume 30, Supplement 9, 2019, Page ix20. https://doi.org/10.1093/annonc/mdz419

  • Bernstock, J. D., Mehari, M., E. Gerstl, J. V. et al. (2025):  Gabapentinoids confer survival benefit in human glioblastoma. Nat Commun 16, 4483 (2025). https://doi.org/10.1038/s41467-025-59614-4

  • Bi, J., Khan, A., Tang, J. et al. (2021): Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug. Cell Rep. 2021 Nov 2;37(5):109957. https://doi.org/10.1016/j.celrep.2021.109957

  • Gallia, G. L., Holdhoff, M., Brem, H., et al. (2020): Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: results of a phase 1 clinical trial. Neurooncol Adv. 2020 Nov 12;3(1):vdaa154. https://doi.org/10.1093/noajnl/vdaa154Bottom

  • Ge, Y., Cao, Y., Wang, Q., Wang, Y., Ma, W. (2024): Impact of antidepressant use on survival outcomes in glioma patients: A systematic review and meta-analysis. Neurooncol Adv. 2024 Oct 26;6(1):vdae181. https://doi.org/10.1093/noajnl/vdae181.

  • Halatsch, M. E., Kast, R. E., Karpel-Massler, G. et al. (2021): A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3. Neurooncol Adv. 2021 Jun 24;3(1):vdab075. https://doi.org/10.1093/noajnl/vdab075

  • Kesari, S., Schiff, D., Henson, J. W. et al. (2008): Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults. Neuro Oncol. 2008 Jun;10(3):300-8. https://doi.org/10.1215/15228517-2008-005

  • Lee, S., Weiss, T., Bühler, M. et al. (2024): High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity. Nat Med 30, 3196–3208 (2024). https://doi.org/10.1038/s41591-024-03224-y

  • Ma, J., Yang, Y. R., Chen, W. et al. (2016): Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells. Oncol Rep. 2016 Aug;36(2):676-84. https://doi.org/10.3892/or.2016.4860

  • Maraka, S., Groves, M. D., Mammoser, A. G. et al. (2019): Phase 1 lead-in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma. Cancer. 2019 Feb 1;125(3):424-433. https://doi.org/10.1002/cncr.31811, Erratum in: Cancer. 2019 Apr 15;125(8):1387. https://doi.org/10.1002/cncr.32021

  • Mastall, M., Roth, P., Bink, A. et al. (2024): A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol. BMC Cancer 24, 82 (2024). https://doi.org/10.1186/s12885-023-11797-z

  • Narita, Y., Ohno, M., Tanaka, S et al. (2025): CTNI-75. Safety and efficacy of metformin and temozolomide targeting cancer stem cells for newly diagnosed glioblastoma. Neuro-Oncology, Volume 27, Issue Supplement_5, November 2025, Page v144, https://doi.org/10.1093/neuonc/noaf201.0570

  • Ohno, M., Kitanaka, C., Miyakita, Y. et al. (2022): Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. Cancers 2022, 14, 4222. https://doi.org/10.3390/cancers14174222

  • Poon, C. C., Hagen, K. M., Sarkar, S. et al. (2026): Niacin Modulates Immune Responses in a Phase I Dose-Escalation Clinical Trial of Newly Diagnosed Glioblastoma. Neurol Neuroimmunol Neuroinflamm. 2026 Mar;13(2):e200530. https://doi.org/10.1212/NXI.0000000000200530

  • Roh, T. H., Moon, J. H., Park, H. H. et al. (2020): Association between survival and levetiracetam use in glioblastoma patients treated with temozolomide chemoradiotherapy. Sci Rep 10, 10783 (2020). https://doi.org/10.1038/s41598-020-67697-w

  • Sesen, J., Dahan, P., Scotland, S.J. et al. (2015): Metformin inhibits growth of human glioblastoma cells and enhances therapeutic response. PLoS One. 2015 Apr 13;10(4):e0123721. https://doi.org/10.1371/journal.pone.0123721.

  • Shishikura, K., et al. (2025): Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma. Sci. Adv.11, eadx7687(2025). https://doi.org/10.1126/sciadv.adx7687

  • Shokr, H., Liao, WC., Faivre-Finn, C. et al. (2025):  Impact of statin use on survival and adverse events in patients with cancer receiving radiotherapy: a systematic review and meta-analysis. BMC Cancer 25, 1666 (2025). https://doi.org/10.1186/s12885-025-15038-3

  • Velho, M. C., Winck, V. L., Mariot, C. D. S. et al. (2025): Scholl JN, Weber AF, Souza RK, Visioli F, Figueiró F, Deon M, Pilger DA, Beck RCR. Intranasal Delivery of Ivermectin Nanosystems as an Antitumor Agent: Focusing on Glioma Suppression. ACS Biomater Sci Eng. 2025 Jul 14;11(7):4231-4244. https://doi.org/10.1021/acsbiomaterials.5c00642

  • Wen, P., Trippa, L., Lee, E.  et al. (2020): CTNI-12. Preliminary Results of the Abemaciclib Arm in the Individualized Screening Trial of Innovative Glioblastoma Therapy (Insight): A Phase II Platform Trial Using Bayesian Adaptive Randomization. Neuro Oncol. 2020 Nov 9;22(Suppl 2):ii44. https://doi.org/10.1093/neuonc/noaa215.179

  • Yoon, W. S., Chang, J.  H., Kim, J. H. et al. (2023): Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Discov Onc 14, 90 (2023). https://doi.org/10.1007/s12672-023-00678-3

  • Bonucci M., Fuggetta M.P., Anelli L., Giannarelli D., Fiorentini C. and G. Ravagnan (2025):  New Approach for Enhancing Survival in Glioblastoma Patients: ALongitudinal Pilot Study on Integrative Oncology. Cancers 2025, 17, 2321. https://www.mdpi.com/2072-6694/17/14/2321

  • Cohen, Z., Maimon, Y., Yoeli-Lerner, M., Yang, P., Samuels, N., Berger, R. (2015): Selective anticancer effects and protection from chemotherapy by the botanical compound LCS101: Implications for cancer treatment. Int J Oncol. 2015 Jan;46(1):308-16. https://doi.org/10.3892/ijo.2014.2711

  • Gentile, M. T., Ciniglia, C., Reccia, M. G. et al. (2015): Ruta graveolens L. induces death of glioblastoma cells and neural progenitors, but not of neurons, via ERK 1/2 and AKT activation. PLoS One. 2015 Mar 18;10(3):e0118864. https://doi.org/10.1371/journal.pone.0118864

  • Koehler, A., Rao, R., Rothman, Y., Gozal, Y. M., Struve. T., Alschuler, L., Sengupta, S. (2022): A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient. Integr Cancer Ther. 2022 Jan-Dec;21:15347354211068417. https://doi.org/10.1177/15347354211068417

  • Ostwal, V., Parulekar, M., Naughane, D et al. (2026): Papaya Leaf Extract to Improve Chemotherapy-Induced Thrombocytopenia: A Phase III Triple-Blinded, Randomized, Placebo-Controlled, Multicentric Trial. JCO Glob Oncol. 2026 Mar;12(3):e2500386. https://doi.org/10.1200/GO-25-00386

  • Rachmut, I. H., Samuels, N., Melnick. S. J. et al.  (2013): Immunomodulatory effects of the botanical compound LCS101: implications for cancer treatment. Onco Targets Ther. 2013 Apr 24;6:437-45. https://doi.org//10.2147/OTT.S42038

  • Rajapakse, S., de Silva, N.L., Weeratunga, P. et al. (2019): Carica papaya extract in dengue: a systematic review and meta-analysis. BMC Complement Altern Med 19, 265 (2019). https://doi.org/10.1186/s12906-019-2678-2

  • Sundarmurthy, D., Jayanthi, C. R., Lakshmaiah, K.,C. (2017):  Effect of Carica papaya leaf extract on platelet count in chemotherapy-induced thrombocytopenic patients: A preliminary study. Natl. J. Physiol. Pharm. Pharmacol. 2017;7:685–692. https://doi.org/10.5455/njppp.2017.7.0202628022017

  • Vengoji, R., Macha, M. A., Batra, S. K., Shonka, N. A. (2018): Natural products: a hope for glioblastoma patients. Oncotarget. 2018 Apr 24;9(31):22194-22219. https://doi.org/10.18632/oncotarget.25175

  • Williams, B. A. (2014): The Role of Supplements (including Anti-Oxidants) in Cancer Treatment. University of California, San Diego, 2014. https://hopefordavid.wordpress.com/wp-content/uploads/2015/06/williamssupplements2014.pdf

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