New tech brings new hope for brain cancer
Cells are the building blocks of our bodies. In fact, the human body has an average of 37 trillion cells – if lined up side by side, that’s enough to circle the earth 19 times! They make up our skin, our bones, our blood, and our brain, with about 200 different types present throughout the body. The cell’s exact job depends on its type. For example, in our brain, we have cells called neurons that are the information messengers, and cells called glia that provide physical support to the neurons by holding them in place and giving them nutrients. You can think of a neuron as being the VIP and glial cells are the personal assistants and bodyguards. But sometimes, the glial cells go rogue and stop supporting the neurons. Instead, they break rules; they multiply and grow relentlessly, pushing and destroying the other cells around them. They have turned from glial cells into a cancerous tumor – a large cellular bully that is virtually immortal.
Figure 1: Diffuse intrinsic pontine glioma is a brain tumor that is located in the pons, a brainstem structure important for breathing, vision, hearing, swallowing, and movement. Image from together.stjude.org.
Glia often go rogue in a brain area called the pons, forming a cancer called diffuse intrinsic pontine glioma, or DIPG (Figure 1). DIPG is the most common form of childhood brain cancer, making up 10 – 20% of all childhood brain tumors and affecting 350 – 400 children across North America and Europe each year. Unfortunately, it is unclear what causes this cancer to arise.
Andrew Deweyert, a researcher and Ph.D. candidate studying DIPG at Western University explained the cruel nature of DIPG, “DIPG is a really devastating childhood cancer, and although we can treat some of the symptoms, we currently have no treatment that can extend the life of children with DIPG.” Because the pons is located deep in the brain and is responsible for vital life functions like breathing, surgical removal of the tumor is impossible. Consequently, there is no effective long-term treatment, leading to a high fatality rate. Very few children survive more than 5 years after diagnosis. While radiation and chemotherapy offer temporary treatments, new methods are needed to improve patient outcomes.
This is where the researchers from Western University come into the picture. Dr. Hebb, Mr. Deweyert, and their colleagues are designing a device that will allow for a new type of therapy, called electrotherapy, which can potentially be used to treat DIPG long-term. The type of electrotherapy their device would provide is called intratumoral modulation therapy (IMT). It uses electric fields to shrink tumors inside the brain. IMT works because cancer cells are naturally more sensitive to electricity than our regular cells. Think of their device as a rescue team with a ray gun (yes, like the science-fiction electro-laser weapon), coming in to kill the glial tumor without damaging the surrounding cells.
So how exactly do researchers rescue the pons from the cancerous glial cells? For IMT to be used to treat DIPG, researchers must design a series of electrodes that can 1) apply an electric field to a whole DIPG tumor (the electrotherapy), and 2) be inserted safely into the brainstem.
In a recent study published in 2019 by Dr. Hebb’s lab, the researchers described how they have achieved step one - they made their ray gun! They first developed an artificial DIPG tumor using real cells from a patient’s tumor and grew it outside the brain in a petri dish. The researchers placed electrodes around the tumor to target it with an electric field. When they turned on the electric field, the number of tumor cells decreased and the tumor shrank. Their ray gun worked! Electrotherapy on its own reduced the number of living tumor cells and when the researchers paired their method with radiation and chemotherapy, the effect was even stronger (Figure 2). Mr. Deweyert is hopeful, “Our work shows that these tumors are actually responding to this new type of treatment modality and it’s a promising first step forward to creating new therapeutics and improving outcomes for these kids.”
Figure 2: Diffuse intrinsic pontine glioma tumors are treated using electrotherapy. Electric fields are generated by electrodes surrounding the tumor to target and kill only tumor cells, leaving good cells alive. Adapted from Deweyert et al., 2019.
The researchers are now working on step 2 – figuring out how to get the rescue team down into the pons to be able to destroy the glial tumor. They first will test out how to target and position electrodes in the brain using a rodent animal model that has a brain tumor in the pons. If they are successful, the researchers hope this treatment can move to clinical trials!
“In the long-term we hope this technology can really broaden the horizons for brain cancer treatment,” said Mr. Deweyert. Because of the way the electrotherapy technology was developed, the researchers can personalize the therapy to uniquely target each person’s tumor. This means that in the future, electrotherapy can be used for other types of primary brain cancer, and even for brain metastases which occur in 20-40% of people with cancer. Brain metastases occur when cancer cells from other types of cancer, like breast, lung, colorectal, or melanoma, spread to the brain. Mr. Deweyert said, “With brain metastases, the prognosis can be much worse than the primary cancer outcomes. That’s why figuring out the intratumoral modulation therapy is so important; it could be used for so many kinds of brain cancer.”
This promising technology designed by the researchers at Western University might make a difference for children with DIPG and people with all types of brain cancer. So maybe cancerous brain tumors, those large cellular bullies, won’t be immortal much longer.
Article: Deweyert A, Iredale E, Xu H, Wong E, Schmid S, Hebb MO. Diffuse intrinsic pontine glioma cells are vulnerable to low intensity electric fields delivered by intratumoral modulation therapy. J Neurooncol. 2019 May;143(1):49-56. doi: 10.1007/s11060-019-03145-8.