What are repurposed drugs for glioblastoma?
A repurposed drug is an approved medicine already proven safe in people. Researchers now test it for a different disease. For glioblastoma, the goal is to use these well-known, lower-cost drugs alongside or after standard treatment. Since we already know the drug is safe in people, researchers can move to clinical trials faster and cheaper than for a new drug. A systematic review found that more than 52 drugs have entered glioblastoma clinical trials through drug repurposing. None has become standard treatment yet, but the pipeline is active and several drugs have reached phase 2 trials.
Why is drug repurposing a priority for GBM?
Glioblastoma is a grade 4 brain tumor. The standard treatment is surgery, radiation, and temozolomide chemotherapy. It extends survival for many patients but rarely eliminates the disease. The blood-brain barrier blocks most conventional drugs from reaching the tumor. New drugs take 10 to 15 years and billions of dollars to develop. Repurposed drugs skip much of that timeline.
Glioblastoma is biologically complex. This adds urgency. Markers like MGMT promoter methylation and IDH mutation status affect how well the tumor responds to standard chemotherapy. Patients with MGMT unmethylated tumors respond poorly to temozolomide. These patients are looking hard for additional options. If you need help understanding your pathology results, our guide explains each key marker and its practical treatment implications.
Which repurposed drugs are being studied for glioblastoma?
The following drugs appear most often in research for GBM. Each has a different mechanism and different level of human proof. Do not start any without oncologist guidance, and check drug interactions with temozolomide, anti-seizure drugs, or steroids first.
Metformin
Metformin is a diabetes medication used by millions. In cancer research, it may disrupt how tumor cells make energy by slowing Complex I of the mitochondrial electron transport chain. Glioblastoma cells need this chain to produce fuel. A 2024 review described how metformin may make glioblastoma cells more vulnerable to temozolomide, which could make standard chemotherapy work better. A phase 2 clinical trial is testing metformin as an add-on therapy in high-grade glioma. Large randomized trial results are limited.
Mebendazole
Mebendazole is a parasite drug used for worm infections. Researchers focus on it because it crosses the blood-brain barrier. Most drugs do not. It may disrupt tubulin, the protein glioma cells need to divide. A 2023 review found that preclinical studies consistently show mebendazole may slow glioma growth and make tumor cells more vulnerable to chemotherapy and radiation. Human trial data are starting to emerge, but not definitive for GBM yet.
Disulfiram
Disulfiram is used to treat alcohol dependence. It slows aldehyde dehydrogenase (ALDH), an enzyme linked to cancer stem cells. These cells may drive treatment resistance in GBM. Research shows disulfiram is often combined with copper, which may boost its anti-tumor effect. The DIRECT randomized trial tested disulfiram plus copper added to chemotherapy in recurrent GBM. Results disappointed compared to lab predictions. Neurological side effects, including fatigue and coordination problems, appeared at higher doses. This shows the gap between lab findings and real patient outcomes.
Valproic acid
Valproic acid is an anti-seizure drug commonly given to GBM patients with seizures. It's also an HDAC inhibitor, which means it may change how genes work in tumor cells. This may give it an anti-tumor effect separate from seizure control. Some past patient records show an association between valproic acid and slightly better outcomes in GBM patients taking temozolomide. Future studies with random assignment are limited. It's unclear if valproic acid truly helps or if the better outcomes came from differences in which patients were chosen for treatment. Research is ongoing.
Chloroquine and hydroxychloroquine
Chloroquine and hydroxychloroquine are antimalarial drugs. They block autophagy, the process where stressed tumor cells recycle their insides to survive treatment. Blocking this may make glioma cells weaker during chemotherapy and radiation. A review found that early trials with chloroquine had mixed results. The review called for stricter patient selection in future studies.
Multi-drug repurposing protocols: CUSP9 and CARE Oncology
Some research groups propose attacking glioblastoma with multiple repurposed drugs at once, hitting several pathways. The CUSP9 protocol combines nine repurposed drugs with low-dose continuous temozolomide for recurrent GBM. Drugs include disulfiram, captopril, sertraline, and artesunate. A proof-of-concept trial tested this approach and informed further research, but CUSP9 is not standard treatment and carries significant drug interaction complexity.
A second widely discussed approach is the CARE Oncology protocol, which combines metformin, atorvastatin (a cholesterol-lowering statin), mebendazole, and doxycycline (an antibiotic). The METRICS study is testing this combination across cancer types including GBM. Results specific to GBM have not been fully published yet.
What the evidence actually shows - and where the limits are
Preclinical research in cell lines and animal models consistently shows these drugs affect glioblastoma cells. The harder question is whether those effects work in patients. For most drugs, we don't know yet.
Key barriers include:
- Blood-brain barrier penetration: a drug that works in a petri dish may not reach the tumor when you take it as a pill.
- Tumor heterogeneity: GBM has multiple subpopulations of cells with different traits. A drug that targets one may miss others.
- Drug interactions: drugs added to temozolomide, anti-seizure drugs, or dexamethasone may affect how well standard treatment works in unpredictable ways.
- Lack of phase 3 data: most evidence comes from phase 1 or 2 trials or from past patient records, which have significant limits and cannot prove cause and effect.
This doesn't mean repurposed drugs have no role. It means the evidence is still developing. Adding them outside a clinical trial carries risk and uncertainty that need expert oversight. Finding the right trial for your tumor profile is often the best option. Our guide walks through how to search ClinicalTrials.gov and which eligibility criteria to look for.
How your molecular profile shapes these discussions
Not every repurposed drug works for every GBM patient. Molecular features of your tumor, like MGMT methylation, EGFR amplification, and PTEN loss, define which pathways are active in your cancer. A tumor suppressor gene is inactivated in PTEN loss. Before discussing off-label drugs, know which pathways are active in your tumor and whether the proposed drug has any lab evidence targeting those pathways.
If you haven't had extended molecular profiling or if your results haven't been discussed for drug selection, getting a second opinion at a specialist center before adding any drugs is sensible. Molecular data changes the conversation a lot.
How to discuss off-label drugs with your oncologist
Bringing up repurposed drugs with your care team takes preparation. These steps help you get a thoughtful answer instead of a dismissal:
- Name the specific drug. Explain what it's normally used for and why it's being studied. For example, explain that metformin is a diabetes drug being tested for how it affects energy in GBM cells, not just "I read about metformin."
- Bring the source. Share the PubMed abstract, clinical trial number, or review you read. This gives your oncologist something to review instead of just hearing it second-hand.
- Ask about drug interactions first. Any drug you add may interact with temozolomide, anti-seizure drugs, or steroids. Ask for a pharmacist to review it, not just a quick verbal check.
- Ask if an open clinical trial exists for this drug in GBM. Trials provide monitoring, may reduce cost, and help future patients. Your oncologist or research nurse can help you find trials.
- Ask what data exists for your tumor profile. A drug studied mainly in MGMT-methylated patients may have no evidence in unmethylated tumors, and vice versa.
- Ask for any off-label drug to be documented and monitored. Ask which blood tests or markers will be tracked, and set a date to decide if you'll continue.
Some patients find this conversation hard because of time pressure or fear of being dismissed. Frame it as wanting to understand the evidence, not demanding a prescription. If your oncologist is unfamiliar with the specific research, ask for a referral to a GBM specialist who follows this work.
If you want your pathology and imaging reviewed by a team with expertise in precision oncology and integrative approaches, you can request a treatment review from the Art of Healing Cancer team. They work with international GBM patients researching off-label options as part of a broader strategy.
Many patients exploring repurposed drugs also ask about over-the-counter supplements. If you want evidence-based options, consider clinically-formulated vitamins and minerals from Ayurnomics. Always tell your oncologist, as some supplements interact with chemotherapy.
If you're ready to share your reports and ask about options, you can upload your MRI and pathology documents through the Glioblastoma Center to request a remote review.
When to talk to your doctor
Talk to your oncologist before starting any repurposed drug, even one that's been used safely for decades. Multi-drug protocols like CUSP9 and CARE Oncology involve significant drug interaction complexity that need expert oversight. If you're at recurrence and feeling pressure to act fast, a specialist review helps separate options worth trying from those unlikely to help at your stage.
This article is for general information and is not a substitute for medical advice. Always consult your oncologist or care team about your specific situation.