Northwestern University Feinberg School of Medicine
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Lou and Jean Malnati Brain Tumor Institute
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Glioblastoma Research

Each year in the United States, more than 13,000 people are diagnosed with glioblastoma. Also called astrocytoma grade IV, glioblastoma is the most common type of glioma, or cancer that starts in the supportive tissue of the brain. It’s also the most aggressive form of cancer that starts in the brain.

Each day at the Malnati Brain Tumor Institute of the Lurie Cancer Center, we work hard to find therapies that will make life longer and better for people who have it.

Surgery alone cannot fully eliminate glioblastoma cells, so discovering new therapies is vitally important. It’s also challenging — for a variety of reasons. One of the biggest reasons is that the brain is protected by a natural barrier that makes it hard for many medicines to reach brain tumors.

Nevertheless, our team of world-renowned scientists and physicians has repeatedly found new ways to prolong survival and improve quality of life for people with glioblastoma. As we build on these advances, we remain focused on our ultimate goal: to cure the disease once and for all.

Building on a strong track record

We’re uniquely equipped for this mission. In 2005, our medical director Roger Stupp, MD, developed what is now the worldwide standard of care for glioblastoma — commonly known as the Stupp protocol. His research showed that a combination of radiation therapy and the chemotherapy drug temozolomide significantly increased survival. Before this discovery, only one in 10 patients lived longer than two years after diagnosis. With the new treatment, the number of patients surviving beyond two years jumped to more than one in four.

In 2017, another of Stupp’s large international studies showed that a treatment called tumor treating fields further prolonged survival. Tumor treating fields are low-intensity, rapidly changing electromagnetic fields that interfere with cell division and prevent tumor growth. (They’re delivered through electrodes worn like a cap and attached to a small, portable device.) With tumor treating fields, more than 43 percent of patients now live longer than two years.

This is not anywhere near enough for us. Our large team of expert physicians and scientists is pursuing several paths that build on the latest scientific discoveries and may lead to new treatments for people with glioblastoma.

Some of our work is already showing promise. The National Cancer Institute recently recognized that promise with an $11.5 million Specialized Program of Research Excellence (SPORE) grant. One of only a handful awarded across the country to brain tumor researchers, the SPORE grant is supporting our push to reach the next breakthrough in care. With this support, we’re turning our discoveries in the lab into clinical trials that give patients new options.

Making oncolytic virotherapy more effective

One of the more promising areas of brain tumor research is oncolytic virotherapy, or viruses engineered to destroy cancer cells. These viruses are commonly injected into tumors, or parts of tumors, that can’t be surgically removed. By infecting the tumor cells, they’re able to break down the tumor, shrinking or even killing it. They also help activate the immune system to fight cancer.

Researchers across the world have tested multiple viruses for the treatment of brain tumors. While some have shown promise, they tend to share a major limitation: A virus injected into a brain tumor doesn’t spread all the way through the tumor.

One of our research teams is dedicated to solving this problem. They’ve developed an oncolytic virus (CARd-Survivin-pK7) that is injected together with neural stem cells. In research on mice, the team found that the neural stem cells helped the virus spread more fully throughout the tumor. As a result, the virus was much more effective against glioblastoma. 

The team is now testing this treatment in a clinical trial for people with malignant brain tumors. The treatment is injected when a neurosurgeon does a biopsy (takes a sample of) or removes part of the tumor. Patients then receive standard chemotherapy and radiation therapy.

Finding the right combination of immunotherapy

Immunotherapy is a type of treatment that helps the immune system fight cancer. But finding immunotherapies that effectively treat glioblastoma has proved challenging. The key, our researchers have discovered, might be using multiple types of immunotherapy together.

One type that has been tested against glioblastoma is immune checkpoint inhibitor treatment. This type of treatment blocks “checkpoints” that stop immune cells from killing tumor cells. Blocking these checkpoints activates the immune system to fight cancer.

Our researchers found that immune checkpoint inhibitors work better when combined with a second immunotherapy. This second immunotherapy blocks an enzyme called IDO1, which suppresses the immune system. Using the two immunotherapies gives the body even more help in fighting cancer.

Combining them both with radiation therapy led to longer survival in mice with brain tumors. Our researchers are now planning a clinical trial to determine whether this combination of treatments will also prolong survival in patients with glioblastoma.

Using nanoparticles to fight glioblastoma

A big challenge in developing new glioblastoma treatments is making sure they can reach the tumor. One promising solution is nanoparticles. These tiny molecules are one to 100 nanometers in size. (A strand of human hair is about 75,000 nanometers in diameter.) As a result, they can be used to carry specific treatments (via injection or IV) to tumor tissues that would otherwise be unreachable.  

At Northwestern University, researchers have engineered a new type of nanoparticle called spherical nucleic acids. Because of their unique three-dimensional architecture, spherical nucleic acids can enter a cancer cell efficiently and change its inner workings.

For example, they can reactivate p53, a tumor-suppressing gene that doesn’t work properly in many patients with glioblastoma. By reactivating the p53 gene, spherical nucleic acids slowed tumor growth in mice with glioblastoma. Now, our researchers are conducting a clinical trial of these nanoparticles for patients with glioblastoma.

Blocking cancer cells from protecting themselves

By the time it’s diagnosed, glioblastoma has typically grown to have billions of cells. Standard treatment kills many of these cells, but some are able to protect themselves. The remaining tumor cells then repopulate the brain with cancer.

One way tumor cells do this is through a process called autophagy, in which they use parts of dying cells to generate energy and grow new cells. Blocking this process can decrease or even eliminate tumor cells that survive the first round of treatment. Our research aims to do just that. And initial results are promising.

Our scientists have discovered that the enzyme ATG4B plays an important role in autophagy by protecting brain tumor cells from being killed by standard treatments. They also discovered an experimental drug that blocks this enzyme. This drug both prolonged survival and made radiation therapy more effective in mice with glioblastoma. Our team is now further developing the drug for use in patients, and will eventually test it in a clinical trial.

Uncovering paths for future research

Alongside our efforts to turn discoveries in the lab into clinical trials that give patients new options, we’re also working constantly to make new discoveries.

For example, our team members are in the early stages of research on the following:

  • Brain tumor vaccines.
  • Genetic mutations that can be targeted with new treatments.
  • A type of immunotherapy that involves the modification of T cells (a type of immune cell that can kill cancer cells).
  • The use of an implantable ultrasound device to temporarily open the blood-brain barrier — a natural barrier that protects the brain but also stops medicines from reaching brain tumors. This will help doctors administer medications that have proven effective in laboratory research but couldn’t otherwise reach brain tumors.

 

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