Breakthroughs in health care over the past few decades have been amazing. Vaccines eradicated small pox, heart transplants have become widespread, and test-tube babies born each year now top 45,000. Yet, for patients with malignant brain tumors, the medical community has had little new to offer.
Survival rates for patients with the highest grade tumors is only about a year — the same it was more than 40 years ago. "Because so little has worked," says health physics professor Steen Madsen, "there's so much more to try — gene therapy, drugs, focal radiation therapy. Researchers are getting very creative because they have to — everything else, everything usual has already been tried."
Madsen and neurosurgeon Henry Hirschberg, an adjunct professor at UNLV, have been working for eight years to figure out how the combination of laser light and light-activated drugs can be used to treat brain cancer.
The current treatment for these tumors is surgery, which removes the bulk of the tumor, but invariably leaves some cancerous cells around the edges. "There's a limit to what you can cut out of the brain," Madsen says soberly. "What it comes down to is that you have to kill the cancer without destroying the patient's quality of life."
After surgery, doctors usually turn to radiation or chemotherapy to kill the remaining cancer cells. But in the brain, the cancer cells happen to be very resistant to radiation. And the same mechanism that protects the brain from toxic substances — called the "blood-brain barrier" — also prevents chemo drugs from reaching the cancer cells hiding among healthy cells. Their initial research in the lab focused on drugs that make cells sensitive to light. Because the blood vessels around the tumor were already damaged — thus that blood-brain barrier was already broken — the drugs leached into the tumor. Laser light was then used to activate the drug and kill the cancer cells.
The research indicated that this technique, called photodynamic therapy (PDT), was very effective at destroying the bulk tumor, but most of the lab rats still died soon after the surgery. "Every time we try something, there seems to be a whole series of new questions," Madsen says. "You go back to your research and you get new ideas."
The duo shifted their investigation to why the lab rats died and found two causes. Some died from edema, a build up of fluid in the brain that is a common side effect of treatment. The others eventually died when new tumors grew from cancer cells that had migrated into healthy parts of the brain.
"Now our question is, 'Can our techniques eliminate those infiltrating cells while minimizing edema reactions?'" Madsen says.
Instead of using the photodynamic therapy to directly kill the cancer cells, Madsen and Hirschberg hope it can be used to help chemo drugs pass through the blood-brain barrier. Opening the barrier can be done with other methods, but because they are not precise, they lead to life-threatening edema.
Once the chemotherapeutic agents have crossed the barrier, the next challenge is to get the agents into the nucleus of the cancer cells. The agents typically stop at the edge of the cellular membrane. The membrane eventually wraps itself around the chemo agent, where it essentially sits in a bubble doing nothing. "Our idea is to inject our light-sensitive agent and a chemo agent at the same time. Then through microsurgery we can very selectively apply laser light, which excites the light-sensitive drug. That destroys the membrane, allowing the chemo agent to reach the nucleus and destroy it," Madsen explains.
The Nevada Cancer Institute recently awarded Madsen and Hirschberg a grant to extend their research into this new area. They've also reached out to community resources for some research tools; Steinberg Diagnostic Medical Imaging has allowed them to use MRI facilities, for example.
If successful in the lab, the researchers' next step would be patient trials, but Madsen doesn't expect a quick breakthrough. "It takes a long time for a new technique like this to go to clinical trials. We hope to get there in the next few years," he says, adding the proposed Nevada Health Sciences Center will help UNLV researchers advance their work.
"I love my work because it challenges me; it forces me to keep learning new things and to learn in more depth," he says. "I find the interaction between physics and biology fascinating, and I suspect there are a lot of puzzles in biology that physics might be able to solve. And as we try to solve those, we might stumble across applications to other diseases."
