People diagnosed with a particularly insidious form of brain cancer, glioblastoma multiforme, typically undergo invasive surgery to remove the malignant tumor, followed by intense courses of radiation and chemotherapy. Some find the treatment regimen is as debilitating as the cancer itself. Today, however, researchers at the Methodist Neurological Institute in Houston, Texas, and Massachusetts General Hospital are testing alternative treatments involving the herpes virus, immunosuppression and nanotechnology in hopes of providing both better outcomes—and quality of life—for people with this deadly form of brain cancer.
Glioblastomas are the most common type of brain tumors seen in adults, and tricky. “I often tell patients glioblastomas are like an octopus,” says David Baskin, a neurosurgeon at the Methodist Neurological Institute. “They have a head that you can easily see but they also have many tentacles that extend long distances into the brain.” This octopus-like quality means that while surgery can move the “head” of the tumor, there are often “tentacles” that cannot be excised—and can therefore continue to cause problems over time. To help mitigate this, neurosurgeons generally follow surgery with six weeks of combined radiation and chemotherapy, a regimen that results in myriad unpleasant neurological and immunological side effects. But even this “shock and awe” treatment extends patients' lives an average of only 14 months.
To offer patients both longer lives and a better quality of life following surgery, Pamela New, a neuro-oncologist at Methodist Neurological Institute, is leading a clinical study that uses the herpes virus to target tumor tentacles.
“This is not your standard herpes virus,” she says. “We’ve manipulated it in the lab—crippled it, really—and turned it into a vector that will seek out the quickly-replicating tumor cells. It finds the tumor cells, and only the tumor cells. And when we apply an anti-viral drug like Valacyclovir, those tumor cells with the virus inside of it die.” Several patients who participated in the initial trial have survived well past the expected 14 months and are faring well.
Alternate delivery: tiny "tubes"
A second therapy harnessing the body’s immune system, or immunotherapy, is also in clinical trials. “The idea is to rev up the immune system in a specific way to target the tumor cells in the brain,” says William Curry, a neurosurgeon at Massachusetts General Hospital. “We can either take the patient’s own blood cells or a particular protein that is only made by the tumor and make a vaccine out of it. We then inject the tumor with the vaccine and it kills the cells.”
Baskin’s laboratory is looking at nanotubes, small carbon clusters approximately a nanometer in size, to target glioblastoma tumors. His group has been able to attach a small antibody to each of these clusters to deliver chemotherapy drugs directly to the inside of a tumor cell. “One of the problems with chemotherapy is that while a good dose can kill your cancer, it can also kill other healthy dividing cells,” he says. “But with these nanotubes, we can selectively deliver an agent to kill the tumor cell only—nothing else.” This method is currently being tested on mice models, injected into the tumor “tentacles” after the body of the mass has been excised. Researchers hope that, like the antibody technique, this method will target only the tumor cells.
“It’s really exciting stuff,” says Baskin. “We are seeing some really significant differences in terms of survival and outcome with these different treatments, which we haven’t seen with just about anything else people have tried in the past. People are living longer and their tumors aren’t growing back right away.”
But Curry cautions that, while promising, none of these treatments offer a cure for glioblastoma multiforme.
”Unfortunately, glioblastoma tumors are almost always going to come back. No single therapy, whether immunotherapy or gene therapy or a viral therapy, is going to cure them,” says Curry. “But we’re trying to figure out what we can do over time to hold them at bay.”