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How does cancer do that? New insights into glioblastomas' diabolical behaviors

Caner Cells
All cancer cells are bad, but few behave as aggressively evasive and invasive as those that make up a glioblastoma, a form of brain cancer.

All cancer cells are bad, but few behave as aggressively evasive and invasive as those that make up a glioblastoma, a form of brain cancer. Now, new research is offering clues into how glioblastoma cells hide from the body’s immune system, giving scientists hope that the insights may lead to more accurate diagnoses and better treatment options.

Like all cancers, glioblastomas are the body's own cells that have mutated and turned traitorous, taking over areas of the brain in a swift and sudden incursion. They grow quickly, creating multiple mutations, signaling pathways and recruiting healthy cells as reinforcements. Once entrenched, these cells are often difficult to find or remove. Surgery may work temporarily, but because these tumors are made of glia (a type of cell found in the central nervous system), they often hide inside brain tissue and out of a surgeon's reach. Chemotherapy, radiation and some targeted therapies are typically used in an effort to roll back or slow the invasion.

What are glioblastomas?

Glioblastomas are the grade IV version of a glioma, a tumor of the brain, brain stem or central nervous system. The tumors often come with a number of symptoms, including headaches, dizziness or nausea, difficulty seeing or speaking and/or seizures. These tumors are sometimes called astrocytomas, for the star-shaped glial cells called astrocytes from which they are formed. Researchers have yet to pinpoint how or why glioblastomas form. "Some of them start off aggressive and keep growing," says Laura Farrington, DO, Medical Oncologist at our hospital near Chicago. "Some of them start as more benign tumors. And over years and years, they get more mutations that make them more aggressive." Some recent studies have shed new light into how and why these rogue cells become devious and devastating.

Researchers in Sweden believe they have discovered one method by which a glioblastoma avoids the immune system. In the results of a study published this year, the scientists concluded that glioblastoma cells create a signaling pathway to communicate with microglia, the brain's immune cells. The signal tricks the microglia into blocking a normally protective protein, causing it to "stimulate the tumor cells instead of attacking them," Bertrand Joseph, the study’s principal investigator, told ScienceDaily. In fact, glioblastomas are sometimes found to be loaded with immune cells, according to an article published this year by the Journal of Clinical Investigation. But as with many cancer cells, those in glioblastomas find ways to either recruit or avoid immune cells or render them less effective. And immunotherapy, a promising treatment that stimulates immune cells against a variety of cancers, has not yet proven useful against glioblastomas.

How are glioblastomas treated?

"The challenge with treating glioblastomas is there are so many cell mutations and so many pathways," Dr. Farrington says. "You can treat one pathway and kill some of the cells, but then they figure out a way around it. Cancer is smart. Cancer is your own body's cells that have just gone haywire and learn to grow and grow." But more mutations also mean more opportunities to attack glioblastomas with insights gleaned from advanced genomic testing. The analyses are used to examine tumors at a molecular level and identify specific mutations that may lead to more targeted treatments. "In a lot of other cancers, we have gene mutations that are not targetable, at least not at the moment," Dr. Farrington says. "In glioblastomas, we have multiple mutations we can target and treat. But these tumors have so many mutations, so we can treat some of them, but it's hard to treat to 12 of them at the same time. That’s what makes treatment so difficult."

Oncologists also have difficulty determining the long-term prognosis for glioblastoma patients because of the unpredictable nature of the cancer’s aggression. In search of more clues, Johns Hopkins Medicine researchers have developed what they call a cellular "racetrack" that allows them to time how fast a glioblastoma cell travels. Preliminary results indicate that the faster the cell, the more aggressive the tumor. Dr. Alfredo Quinones-Hinojosa at the Johns Hopkins University School of Medicine suggests these tests may one day lead to more accurate diagnoses and "provide useful updates, inform treatment choices and perhaps develop new treatments faster."

In the search for better treatments and prevention strategies, scientists are learning more about how cancer grows and survives, even in the most hostile environments. This blog is an installment in an occasional series called “How does cancer do that?” designed to shine a spotlight on newly discovered cancer behaviors that add to our growing understanding.

Learn more about glioblastoma, its symptoms and the treatments used to fight it.