Cancer Expert MD

Glioblastoma is the most common and most aggressive brain cancer in adults. Standard treatment is surgery to remove as much tumor as safely possible, followed by radiation with temozolomide chemotherapy, and median survival has long been about 15 to 17 months. Progress has been slow, because the blood-brain barrier keeps most drugs out of the brain and because each tumor is made of many different kinds of cells. Several approaches have now extended survival in clinical trials, and newer ones are showing promise. This article explains them, the tests every patient should have, and the integrative and repurposed-drug approaches that have been tested in people.

The Tests Every Patient Needs

MGMT methylation. MGMT is a DNA-repair gene. When it is switched off, or methylated, temozolomide works better and survival is longer. This single test shapes many treatment choices.

IDH mutation. Tumors with an IDH mutation are now classified as a different disease, IDH-mutant astrocytoma, with a better outlook. For lower-grade IDH-mutant tumors there is a targeted pill, vorasidenib.

Full tumor sequencing. DNA and RNA sequencing can find targets such as BRAF V600E mutations and gene fusions, which have effective targeted drugs, and EGFR changes that newer cell therapies attack. See our article on tumor DNA and RNA sequencing.

Surgery: Making the Tumor Glow

German neurosurgeons developed fluorescence-guided surgery. Before the operation, the patient drinks 5-aminolevulinic acid, which makes tumor cells glow pink under blue light so the surgeon can see the edges of the tumor. In the German randomized trial led by Walter Stummer, all visible tumor was removed in 65 percent of patients, compared with 36 percent with standard surgery, and twice as many were free of progression at six months, 41 percent compared with 21 percent.¹

Standard Treatment, and a German Improvement

Since 2005, standard treatment after surgery has been six weeks of radiation with daily temozolomide, followed by six months of temozolomide.²

For patients whose tumors are MGMT-methylated, the German CeTeG/NOA-09 trial, led by Ulrich Herrlinger in Bonn, found that adding a second chemotherapy drug, lomustine, to temozolomide extended median overall survival to 48.1 months, compared with 31.4 months with temozolomide alone.³

Tumor Treating Fields

Tumor Treating Fields (Optune) are low-intensity electric fields delivered through patches worn on the shaved scalp, which disrupt dividing cancer cells. In the EF-14 trial, adding them to maintenance temozolomide extended median overall survival to 20.9 months, compared with 16.0 months, and five-year survival to 13 percent, compared with 5 percent.⁴

In June 2026, the TRIDENT trial of 981 patients found that starting the device earlier, during radiation, did not extend survival further, 17.7 months compared with 17.5 months. Starting it after radiation remains the standard.⁵

New in 2025 and 2026

Opening the blood-brain barrier with focused ultrasound. It is estimated that less than 20 percent of temozolomide reaches the brain. In a multicenter trial led by the University of Maryland and published in The Lancet Oncology in November 2025, patients had focused ultrasound with injected microbubbles to open the blood-brain barrier temporarily before each dose of maintenance temozolomide. Median overall survival was 31.3 months, compared with 19.3 months in 185 closely matched patients treated without ultrasound. Because the comparison group was matched rather than randomized, larger trials are now under way.⁶

A personalized vaccine. DCVax-L is made from a patient’s own immune cells, called dendritic cells, loaded with proteins from his or her own tumor. In a phase 3 trial of 331 patients, median survival in newly diagnosed glioblastoma was 19.3 months, compared with 16.5 months in outside control patients, and five-year survival was 13 percent, compared with 5.7 percent.⁷ Because the comparison was with outside controls, the size of the benefit has been debated. A reanalysis presented at the British Neuro-Oncology Society in July 2026 suggested it may be larger than first reported.

CAR-T cells. At the University of Pennsylvania, CAR-T cells engineered to attack two targets on glioblastoma cells, EGFR and IL13Rα2, were delivered directly into the fluid around the brain. They shrank tumors in most patients with recurrent glioblastoma, and several patients lived 12 months or longer. The shrinkage was often temporary, and the research continues.⁸

A cancer-killing virus approved in Japan. Teserpaturev (Delytact), a modified herpes virus injected into the tumor, was approved in Japan in 2021 after a University of Tokyo trial in which 84 percent of patients with residual or recurrent glioblastoma were alive one year later.⁹

Integrative and Repurposed-Drug Approaches Tested in Glioblastoma

Nine repurposed drugs at once (CUSP9v3). At Ulm University Hospital in Germany, Marc-Eric Halatsch and colleagues combined nine drugs approved for other conditions, aprepitant, minocycline, disulfiram, celecoxib, sertraline, captopril, itraconazole, ritonavir and auranofin, with low-dose daily temozolomide in 10 patients with recurrent glioblastoma. Under careful monitoring the regimen was safe, and half the patients were free of progression at 12 months, well above what is typical for recurrent disease. A randomized trial is being prepared.¹⁰ See our guide to repurposed drugs and mebendazole, which has been studied in brain tumors.

Boswellia (frankincense) for brain swelling. In a German placebo-controlled trial of 44 patients receiving radiation for brain tumors, Boswellia serrata reduced brain swelling by more than 75 percent in 60 percent of patients, compared with 26 percent with placebo, which may reduce the need for steroids.¹¹

Ketogenic diet. In Frankfurt’s ERGO2 trial, a calorie-restricted ketogenic diet with short fasting periods during re-irradiation for recurrent brain tumors was safe, but did not significantly improve progression-free survival at six months.¹² A randomized multi-site trial of a ketogenic diet in newly diagnosed glioblastoma is now under way in the United States. See the ketogenic diet and cancer.

Chloroquine. In a small Mexican trial of 30 patients, the antimalarial drug chloroquine added to standard treatment was associated with a median survival of 24 months, compared with 11 months, but the difference was not statistically certain.¹³

Hyperbaric oxygen. Japanese researchers have given radiation immediately after hyperbaric oxygen to overcome the low oxygen levels that make glioblastoma resistant to radiation. See our article on hyperbaric oxygen therapy and cancer.

How Cancer Expert MD Helps

Cancer Expert MD specializes in education and consultation for people with Stage IV and metastatic cancer. Our guide to what to do when chemotherapy stops working explains re-testing and the next steps, and our book, The New Reality of Cancer, covers testing and treatment across all cancers.

Frequently Asked Questions

What is the most important test in glioblastoma?

MGMT methylation. When MGMT is switched off, temozolomide works better, and adding lomustine extended median survival to 48.1 months in a German trial. IDH testing and full tumor sequencing are also essential.

Do Tumor Treating Fields help?

Yes. In the EF-14 trial, adding them after radiation extended median survival from 16.0 to 20.9 months. Starting them earlier, during radiation, did not add further benefit in the 2026 TRIDENT trial.

Can focused ultrasound help chemotherapy reach the brain?

Early results are encouraging. In a 2025 trial, opening the blood-brain barrier before each dose of temozolomide was linked to a median survival of 31.3 months, compared with 19.3 months in matched patients. Randomized trials are under way.

Are repurposed drugs used for glioblastoma?

Yes. The German CUSP9v3 protocol combines nine repurposed drugs with low-dose temozolomide, and half of the patients in its first trial were free of progression at 12 months. A randomized trial is being prepared.

---

More articles on cancer types and all articles.

References

1. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. The Lancet Oncology. 2006;7(5):392–401.
2. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine. 2005;352(10):987–996.
3. Herrlinger U, Tzaridis T, Mack F, et al. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. The Lancet. 2019;393(10172):678–688.
4. Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306–2316.
5. Novocure. Topline data from the phase 3 TRIDENT trial (EF-32) of Tumor Treating Fields started during chemoradiation in newly diagnosed glioblastoma. June 18, 2026.
6. Woodworth GF, et al. Focused ultrasound opening of the blood-brain barrier with maintenance temozolomide in newly diagnosed glioblastoma. The Lancet Oncology. 2025.
7. Liau LM, Ashkan K, Brem S, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncology. 2023;9(1):112–121.
8. Bagley SJ, et al. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial. Nature Medicine. 2025;31(8):2778–2787.
9. Todo T, Ito H, Ino Y, et al. Intratumoral oncolytic herpes virus G47Δ for residual or recurrent glioblastoma: a phase 2 trial. Nature Medicine. 2022;28(8):1630–1639.
10. Halatsch ME, et al. A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3. Neuro-Oncology Advances. 2021.
11. Kirste S, Treier M, Wehrle SJ, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117(16):3788–3795.
12. Voss M, Wagner M, von Mettenheim N, et al. ERGO2: a prospective, randomized trial of calorie-restricted ketogenic diet and fasting in addition to reirradiation for malignant glioma. International Journal of Radiation Oncology, Biology, Physics. 2020;108(4):987–995.
13. Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine. 2006;144(5):337–343.

This article is for education only. It is not medical advice and does not diagnose or treat any condition. Cancer Expert MD has no financial relationship with any laboratory, drug maker, supplement company, clinic or hospital.