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The Life of a Brain Tumor: How Does Glioblastoma Grow?

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a female doctor or surgeon is analyzing the digitally generated scans of a human brain

Out of roughly 130 different types of brain and central nervous system tumors, glioblastoma is among the most common and most lethal. On average, 15,000 new cases of glioblastoma are diagnosed each year, and life expectancy hovers in the area of 14 months.

Glioblastoma is also one of the most well-known forms of brain cancer, having made headlines in recent years in connection with high-profile political figures like Beau Biden, Ted Kennedy and John McCain, all of whom died of the disease within years of diagnoses.

However, despite its notoriety, how much does the general public really know about glioblastoma? We asked Stephen Bagley, MD, an Assistant Professor of Medicine here at Penn, to walk us through the life of brain tumors like glioblastoma, including how they start, how they grow and what happens to them during the treatment process.

The Birth of a Brain Tumor

The first spark of glioblastoma in the brain — or the “tumor-initiating event,” as Dr. Bagley put it — remains something of a mystery to medical experts.

“In the vast majority of cases,” the beginnings of glioblastoma are unknown, Dr. Bagley said. “We presume there is an initial molecular event in one cell that sets the process of becoming an actual cancer into motion,” but evidence of this initial event is scant.

Following this tumor-initiating event, “additional sequential mutations” take place within the tumor cell’s DNA. As the mutations accumulate, “the cells begin to take on more of a malignant behavior. They gain the ability to grow uncontrollably and invade healthy tissues, which is the hallmark of cancer.”

How Does the Brain Tumor Spread?

There are basically two ways cancer cells can grow.

The first way “is that they take up shop in one part of the brain and continue to grow as a mass — what we think of conventionally as a tumor,” said Dr. Bagley. Defined broadly, a tumor is a lump of abnormal cells that takes on “a roundish shape, like a ball. It’s what the surgeon can see when they’re operating. It’s what we can see on an MRI.”

But the visible tumor is “only the tip of the iceberg,” Dr. Bagley said. “Underneath that visible portion there is more tumor that is growing in a vague, invasive and migratory fashion.” In addition to forming a noticeable lump, “the tumor cells can actually migrate along neural pathways” in the brain. Like a complex network of highways, these neural pathways allow ”tumor cells to travel to the other side of the brain. So you could end up with the disease on both sides of your brain — or really at any location in the brain.”

“That’s part of what makes glioblastoma so difficult,” Dr. Bagley continued. “You can do surgery on the one main mass, but if any of those cancer cells have already migrated away from the primary mass, then you’re dealing with what we call a diffuse disease of the brain,” meaning the cancer has significantly spread itself out around the brain.

What Happens to the Tumor During Cancer Treatment?

Aside from complex neurosurgery, the gold-standard treatment approach in the fight against aggressive brain tumors involves a combination of chemotherapy and radiation therapy.

“The tumor cells that are actively growing — the ones that are in the process of dividing and growing — those are the tumor cells that respond well to chemo and radiation,” said Dr. Bagley. Those treatment methods are the most capable of damaging tumor DNA.

Damaging the tumor cells that are actively growing is “good because you’re going to shrink the tumor,” he added.

However, what’s so difficult about treating brain tumors like glioblastoma is “there’s also a population of cancer cells that are not actively growing or dividing.” Those cells, known as cancer stem cells, “are just sitting in the tumor, dormant. And because they’re not dividing, they don’t die when exposed to chemotherapy and radiation.”

Cancer stem cells could remain in a dormant state “anywhere from months to many years, depending on the tumor type and how effective the treatment was,” said Dr. Bagley. “But it’s that population of cancer stem cells that eventually reseeds the tumor and results in relapse.”

The Future of Brain Tumor Treatment

Suffice it to say, making headway in the fight against glioblastoma means developing treatment methods that target and destroy cancer stem cells.

Through drug therapies like immunotherapy, which reprograms the immune system to identify and attack cancer cells, “those stem cells should be recognized as foreign to the immune system. So you can potentially eradicate them,” said Dr. Bagley.

Immunotherapy, which is being pioneered here at Penn under the leadership of Donald M. O’Rourke, MD and Arati S. Desai, MD, is a beacon of hope in the fight against glioblastoma.

Currently in clinical trials at Penn, Dr. Bagley referred to immunotherapy as an “exciting and promising” new form of cancer treatment.

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