Can Old Treat New?



Glioblastoma multiforme (GBM) has recently made headlines for both its lethal effects and the discovery of potential new life-saving treatments. A grade IV brain tumor, GBM is typically very aggressive, spreads quickly and is highly malignant. The average survival rate is 14 months to two years.

“Glioblastomas differ from other brain tumors because its primary origin is in the brain. It typically also doesn’t metastasize outside of the brain,” says Dr. Kiran Prabhu, a board certified radiation oncologist with INTEGRIS in Oklahoma City.

“Symptoms often exhibit very rapidly and can include headaches, nausea and vomiting from intracranial pressure as well as seizures and partial paralysis. The type of symptoms a patient experiences may vary upon which part of the brain the tumor is in. Glioblastomas also have tentacles that invade the adjacent brain tissue which makes complete removal of the tumor very difficult.”[pullquote]“The goal of surgery is to make a tissue diagnosis with biopsy and hopefully – if the anatomical situation allows for surgical removal or debulking of the tumor – to reduce the cancer burden in the brain,”[/pullquote]

Over the years, Dr. Patrick P. Han has worked with many GBM patients. He is a board certified neurosurgeon and the medical director at St. John Neuroscience Institute in Tulsa. He is also the co-medical director at St. John Heyman Stroke Center.

“Glioblastoma multiforme arises largely from astrocytes, which are the supportive cells of the brain that provide nutrition and protection for neurons, the functional cells of the brain. Normally, these astrocytes help form the blood-brain barrier, which plays a protective role. In the case of treating GBM, however, delivery of chemotherapy becomes very difficult because the blood-brain barrier can prevent the passage of chemotherapy agents to the tumor,” says Han. “In addition, the tumor grows rapidly and spreads along the white matter pathways of the brain, making surgical resection difficult.”

Han says the tumor can grow to a large size before symptoms emerge, which can make operating on the tumor very risky.

He adds that unlike other areas of the body that allow for much more aggressive surgical removal with margins, such as a nephrectomy for kidney cancer or a mastectomy for breast cancer, the aggressive surgical removal of GBM is not largely performed in adult patients because of the risk of neurological complications. However, Han says the current typical treatment for GBM includes surgery followed by radiation and chemotherapy.

“The goal of surgery is to make a tissue diagnosis with biopsy and hopefully – if the anatomical situation allows for surgical removal or debulking of the tumor – to reduce the cancer burden in the brain,” says Han.

While there is ongoing research and various clinical trials for GBM treatments, the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center recently earned attention for its Phase I clinical trial for recurrent GBM patients and its use of the poliovirus – specifically PVS-RIPO.

Han explains that PVS-RIPO is a genetically engineered poliovirus that has had a piece of genetic code of a cold-causing rhinovirus spliced into the poliovirus genome.

“PVS-RIPO is being directly injected into recurrent GBM in humans with encouraging early results,” says Han. “This PVS-RIPO naturally infects almost all cancer cells because the receptor for poliovirus is abnormally present on most tumor cells. PVS-RIPO kills tumor cells but not normal cells based on specific biochemical abnormalities only present in cancer cells.”

As these clinical trials continue, the ultimate goal is to establish PVS-RIPO as a possible therapy for brain tumors.

“The immunotherapy at Duke University is very promising,” says Prabhu. “At first there was only surgery to treat this tumor, but then we added radiation followed by chemotherapy, which really changed the paradigm for treating GBM. We are learning more about tumors at a molecular level, and with this knowledge we’ll hopefully be able to provide new treatments, help increase survival rates and offer patients a better quality of life.”