Electric Fields May Help Beat Brain Cancer’s Worst Form

Electric fields delivered through electrodes placed on the scalp could unlock the power of immunotherapy against glioblastoma, the deadliest form of brain cancer.

New research from USC shows that combining this electric field therapy with immunotherapy and chemotherapy extended survival by 70% compared to previous treatments. The finding offers particular hope for patients with large, inoperable tumors who face the bleakest prognosis—these patients lived 13 months longer than expected and showed the strongest immune responses to treatment.

A New Weapon Against an Unforgiving Enemy

Glioblastoma strikes with devastating efficiency. The average survival time after diagnosis is just eight months, according to the National Brain Tumor Society. Even with aggressive treatment including surgery, radiation, and chemotherapy, fewer than 15% of patients survive five years.

The challenge lies partly in glioblastoma’s location. These tumors grow within the brain, protected by the blood-brain barrier that normally shields neural tissue from harmful substances. Unfortunately, this same barrier blocks many cancer-fighting immune cells and treatments from reaching their target.

“By using TTFields with immunotherapy, we prime the body to mount an attack on the cancer, which enables the immunotherapy to have a meaningful effect in ways that it could not before,” said Dr. David Tran, chief of neuro-oncology at Keck Medicine and the study’s corresponding author.

How Electric Fields Fight Cancer

Tumor Treating Fields (TTFields) represent a fundamentally different approach to cancer treatment. Instead of using drugs or radiation, the therapy delivers low-intensity electric fields directly into tumors through arrays of electrodes placed on the patient’s scalp.

These alternating electric fields create chaos inside cancer cells. They push and pull key cellular structures in constantly shifting directions, making it nearly impossible for tumor cells to divide and multiply successfully. Patients wear the mesh electrodes approximately 18 hours daily, receiving precise frequencies calibrated to their specific tumor location.

But TTFields do more than just disrupt cancer cell division. The electric fields attract tumor-fighting T cells—white blood cells that identify and attack cancer—into the tumor area. When combined with immunotherapy, these T cells remain active longer and get reinforced by even more effective cancer-fighting cells.

Key Study Results:

• 70% increase in overall survival with the triple therapy combination
• Patients with inoperable tumors lived 13 months longer than expected
• Only 7.5% of treatment-related side effects were severe
• Larger tumors showed stronger immune responses to treatment
• Electric fields specifically activated immune pathways in dendritic cells

The Surprising Advantage of Inoperable Tumors

Conventional wisdom suggests that removing as much tumor as possible gives patients the best chance of survival. But this study revealed something unexpected: patients whose tumors were too large or dangerous to remove surgically actually responded better to the electric field treatment.

Seven patients with biopsy-only tumors—meaning surgeons could only take tissue samples rather than remove the cancer—showed remarkable improvements. Two achieved near-complete responses, two reached partial responses, and two maintained stable disease for extended periods.

The research team discovered why larger tumors responded so dramatically. The study’s immune monitoring revealed that electric fields work by triggering what scientists call “in situ immunization”—essentially turning the tumor itself into a vaccine factory. Larger tumors provide more targets for this immune activation, creating a more robust anti-cancer response.

Molecular Mechanisms Behind the Success

The research went far beyond measuring survival times. Using advanced techniques including single-cell RNA sequencing, the team tracked how the treatment affected patients’ immune systems at the molecular level—an important detail missing from press coverage.

They discovered that electric fields specifically activated the type I interferon pathway in dendritic cells—specialized immune cells that act as generals commanding the body’s cancer-fighting forces. This activation occurred within four weeks of starting electric field therapy, before immunotherapy was even added to the treatment regimen.

The interferon pathway then triggered T cell activation and expansion, creating an army of cancer-fighting cells. When immunotherapy was added, it sustained and amplified this immune response, leading to what researchers called “adaptive replacement” of T cell populations with increasingly effective cancer fighters.

A Team Sport Against Cancer

Dr. Tran used a sports analogy to explain how the combination works: “Think of it like a team sport—immunotherapy sends players in to attack the tumor (the offense), while TTFields weaken the tumor’s ability to fight back (the defense). And just like in team sports, the best defense is a good offense.”

This teamwork approach addresses a fundamental problem with treating brain cancer. Immunotherapy drugs like pembrolizumab have revolutionized treatment for many cancers, but they’ve largely failed against glioblastoma. The brain’s immune-privileged environment, combined with glioblastoma’s ability to suppress immune responses, renders these powerful drugs ineffective when used alone.

When Tumors Fight Back

The study also revealed how glioblastoma adapts to evade treatment—insights that extend well beyond typical research summaries. When researchers analyzed recurrent tumors from patients whose cancer eventually returned, they found a sophisticated resistance mechanism.

The tumors had essentially rewired their molecular defenses. While the PD-1/PD-L1 immune checkpoint targeted by pembrolizumab was downregulated, alternative immune checkpoints like TIM-3, VISTA, and CD276 were significantly upregulated. This suggests the cancer learned to escape treatment by switching to different molecular escape routes.

This finding could guide future treatment strategies. Rather than targeting just one immune checkpoint, doctors might need combination approaches that block multiple escape routes simultaneously.

Moving Toward Larger Trials

The encouraging results have prompted a larger Phase 3 clinical trial now enrolling patients at 28 sites across the United States, Europe, and Israel. This study aims to enroll over 740 patients through April 2029, including those with varying degrees of surgical tumor removal.

“Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option,” Tran noted.

The research represents more than just another treatment combination. It demonstrates how understanding cancer biology at the molecular level can reveal unexpected therapeutic opportunities—transforming what seemed like a disadvantage (inoperable tumors) into a treatment advantage.

For the roughly 25% of glioblastoma patients whose tumors cannot be safely removed, this research offers something previously in short supply: hope grounded in rigorous science and a clear understanding of why the treatment works.