Brain tumor growth can be slowed, new study suggests

For most patients with a common brain tumor, the outlook is grim. Aggressive and stubborn, glioblastoma is hard to wipe out with surgery, radiation or chemotherapy.

Now, a group that includes University of Florida Health researchers has found a way to improve survival time in a mouse model by halting the tumor's spread. It's the first time scientists have manipulated successfully the signals in a cell that allow it to contract in order to impede a brain tumor's growth. The approach makes it harder for the cell to squeeze through surrounding tissue, keeping the tumor in check.

The treatment method boosted survival time for glioblastoma multiforme by 30 percent during testing.

Three UF Health researchers took part in the study, published in the journal Cancer Research. Its lead author is Sanjay Kumar, M.D., Ph.D., a professor of bioengineering at the University of California, Berkeley.

Glioblastoma is the most common brain tumor in adults. There is no effective long-term treatment and patients usually live for 12 to15 months after diagnosis, according to the National Cancer Institute.

The findings are significant because current glioblastoma treatments are difficult and typically don't eradicate the tumor, said Loic P. Deleyrolle, Ph.D., a research assistant professor in the department of neurosurgery at UF's College of Medicine who participated in the study. The glioblastoma tumor is known for spreading to many parts of the brain, making surgery a challenge. Chemotherapy isn't effective for very long because almost all brain tumor patients develop resistance, and approximately 50 percent are resistant prior to treatment.

"Surgery tends to be the best way to remove a tumor, but it always comes back. Chemotherapy will never wipe away the tumor cells. We needed something else," Deleyrolle said.

To do that, the research team looked for a way to manage the disease by slowing a tumor's advancement. The study focused on targeting a protein, myosin II, to control the way a cell moves, invades and seeds tumors, Kumar said.

The protein stiffens a part of the tumor-initiating cell and affects the way it contracts, researchers found.

This is some of the first direct evidence that tumor progression can be slowed and survival improved by manipulating the way a cell mechanically "senses" its surroundings, Kumar said. The survival rate increased because the tumor cells did not migrate across the brain as they normally would.

"There's only so much room in the skull, and as soon as the tumor tissue takes over the brain tissue, it can cause neuronal cell death," said Regina Martuscello, a UF predoctoral fellow and graduate assistant in neurosurgery who worked on the study. "Reducing infiltration and invasion of tumor cells could ultimately increase patients' survival,"

Because it's so difficult to eradicate glioblastoma, keeping it contained is especially critical. It's that prospect that has researchers so intrigued by the findings, though Kumar said much more study is needed to prove its effectiveness as a treatment.

Still, the goal is to make brain tumors like glioblastoma less deadly and more manageable.

"When you reduce the invasive aspect of a tumor cell, you can reduce the damage to the patient and potentially extend their lifespan," Martuscello said.

UF Health researchers joined the project partly because Brent Reynolds, Ph.D., an associate professor of neurosurgery in UF's College of Medicine, has exceptional expertise in isolating cells needed for the research from patient tumors, Kumar said. The collaboration began in 2009, and the findings would not have been possible without "considerable" intellectual input and guidance from the UF researchers, he said.