Ученые Университета Западного Онтарио создали метод лечения глиобластомы с помощью динамических электрических полей

More than a decade ago, Dr. Matthew Hebb was treating patients with Parkinson's disease using deep brain stimulation by implanting tiny electrodes into the brain and delivering electrical signals to control tremors. He wondered if the same basic technology could be used against brain cancer. Hebb, neurosurgery professor at Western University's Schulich School of Medicine & Dentistry, took tumour samples removed during surgery back to his laboratory, implanted electrodes and stimulated the cancer cells. The tumours responded. That unexpected observation set in motion years of research into what is now called Intratumoral Modulation Therapy, or IMT - an original approach that uses low-amplitude electric fields to disrupt the growth of glioblastoma, one of the most aggressive and difficult-to-treat brain cancers. Now, a Western-led research team has taken another step toward potentially bringing the technology from the laboratory to patients. The latest study, published in Neuro-Oncology Advances, shows that IMT can safely deliver stronger, dynamic electric fields directly to a glioblastoma tumour while significantly slowing brain tumour growth, in an animal model. The research team, which included Hebb, physics and astronomy professor Eugene Wong, medical biophysics professor Terry Peters, anatomy and cell biology professor Susanne Schmid and postdoctoral researcher Erin Iredale, observed an eight-fold reduction in tumour growth measured through bioluminescence and a five-fold reduction in tumour volume measured by magnetic resonance imaging (MRI) after seven days of treatment. For Iredale, the first author on the study and has worked on the IMT project since her undergraduate degree, the results represent another important step toward a treatment she hopes could one day help patients. "It's so interdisciplinary," said Iredale. "We need everyone from different fields, with their own expertise, to come together to solve this huge problem in health care." Different kind of electrical treatment Glioblastoma is a devastating cancer that begins in the cells or tissues of the brain. Even with current treatments, including surgery, radiation and chemotherapy, patients diagnosed with the disease have a median survival of just more than a year. One of the challenges is that glioblastoma cells divide rapidly despite aggressive conventional treatments, leading to recurrence mainly near the site of the surgery. IMT takes direct aim at that process. Rather than using electricity to acutely burn or destroy the tumour, the treatment delivers chronic low-amplitude electric fields that interfere with the way cancer cells divide. "When we put this electric field on those cells, it prevents them from dividing properly," said Iredale. "So, they're kind of stalled in their cell division process." The exact biological mechanisms are still being investigated, but the team has repeatedly observed reduced tumour growth when the electric fields are applied. The idea grew from Hebb's early experiments and then expanded as physicists and biomedical researchers joined the project. Deep brain stimulation normally operates at frequencies designed to produce a neurological response. For cancer treatment, however, the goal is different. The researchers increased the frequency so the stimulation could target the tumour without producing unwanted effects in normal brain tissue. The result is a treatment designed to destroy the cancer while leaving the surrounding brain largely undisturbed. Finding the sweet spot Iredale joined the IMT project in 2016 as an undergraduate student when she was studying medical physics and applied mathematics. She was drawn to the possibility of combining physics and mathematics with the practical goal of helping patients - an interest that eventually led to a PhD in medical biophysics, where her research focused on developing a treatment-planning system for IMT. Iredale's work in the Hebb lab has helped address one of the central challenges of treating a tumour inside the brain: precisely controlling where the electric field goes and how strong it is. The latest study, done in rats, marks the first time the team used multiple electrodes in a living brain to create a dynamic electric field. Three electrodes were implanted around the tumour. By shifting the phase of the electrical signals delivered by each electrode, the researchers created an electric field that rotates over time. The approach helps cover the tumour more completely, reducing the possibility of 'cold spots' where cancer cells might escape treatment. "We're basically triangulating the tumour," said Iredale. "We're using the electrodes to target very specific areas, making sure the electrical stimulation reaches the tumour while delivering the right amount of energy to each spot." - Western postdoctoral researcher Erin Iredale The researchers used computational modelling to determine how the fields would be distributed through the brain and then confirmed those predictions with direct electrical measurements. Importantly, the treatment produced no neurological adverse effects or imaging evidence of brain injury. From computer models to the clinic The new treatment-planning system, devised by Iredale, is designed to eventually help physicians personalize IMT for individual patients. A physician could provide a patient's MRI, and the system would calculate where electrodes should be implanted and what stimulation parameters should be used to provide the necessary tumour coverage. The system currently relies on traditional computational methods, including an optimization algorithm developed by Iredale. Artificial intelligence and machine learning could potentially be incorporated in the future. The research has progressed from studies in cancer cells to animal models, and while further work will be required before the treatment can be tested in people, the team is already developing a prototype with the goal of moving toward a first-in-human clinical trial. "In five to 10 years, I would hope to see IMT go through an initial clinical trial to test its efficacy against glioblastoma," said Iredale. "From there, we could start to see it become part of the treatment options available to patients with brain cancer." Learn more about how Western is optimizing health for all.