LAS VEGAS - July 9, 2009 - For patients with brain cancer, treatment options - and ultimately survival rates - are limited by the inability of most anti-cancer drugs to cross the blood-brain barrier, a natural cluster of cells that prevents toxic substances from reaching the brain.
In a study published this month by the Journal of Neuro-Oncology, a team of researchers from UNLV, Nevada Cancer Institute and University of California, Irvine reveal the effectiveness of photochemical internalization (PCI), a promising new technique that allows for targeted chemotherapeutic treatment of brain tumor cells by selectively opening the blood-brain barrier. The study, though years away from human clinical trials, is the first step toward addressing an issue that has stymied advancements in brain cancer treatment for decades.
In many cases, malignant brain tumors recur close to where they are surgically removed; 80 percent of the time they recur within a few centimeters of their site of origin.
According to Steen Madsen, UNLV Health Physics professor and one of the lead investigators on the study, current techniques to disrupt the blood-brain barrier inadvertently expose the entire brain to other potentially harmful toxins. PCI, on the other hand, allows for targeted disruption of the barrier by combining light activated drugs, or photosensitizers, with drugs known to disrupt the blood-brain barrier. This limits the flow of harmful toxins and paves the way for chemotherapy to reach the brain more efficiently.
"PCI is different than many current cancer treatment approaches in that it addresses the blood-brain barrier issue by delivering therapeutic agents to targeted areas of the brain," said Madsen. "This targeted delivery could make PCI potentially useful as a treatment not only for brain cancer but for a variety of neurological conditions, such as Alzheimer's and Parkinson's diseases."
In PCI, photosensitizers are injected into the patient. This is followed by an injection of a drug known to disrupt the blood-brain barrier. The photosensitizers surround the drug molecules and prevent them from infiltrating the entire brain. Then, a specific wavelength of light therapy is focused on the target area, activating the photosensitizers and releasing the barrier-busting molecules. With the barrier now selectively, yet temporarily, opened, chemotherapy can be administered to the targeted areas.
To test the effectiveness of chemotherapy treatment combined with PCI, researchers used rats segmented into three groups; one receiving PCI and chemotherapy, one receiving traditional chemotherapy treatment without PCI, and one receiving no treatment. Of the group administered PCI and chemotherapy, more than 60 percent survived more than 70 days, far surpassing either of the other two groups. The findings suggest that, under the appropriate conditions, PCI is a promising method to selectively disrupt the blood-brain barrier for treatment.
Researchers note that while PCI-aided delivery of chemotherapy to the brain has proven effective in laboratory tests, additional testing prior to human clinical trials is needed to identify other less-toxic blood-brain barrier agents to be used in tandem with the photosensitizer in the PCI process.
The study was funded through the Nevada Cancer Institute's Collaborative Grant Program and appeared in the Online First section of the Journal of Neuro-Oncology: . Participating in the study with Madsen were Henry Hirschberg, UNLV health physics adjunct professor and research professor with the University of California, Irvine's Beckman Laser Institute; UNLV graduate researchers Michelle Zhang and David Chighvinadze; Michael Gach from Nevada Cancer Institute; Francisco Uzal from the University of California, Davis; Qian Peng from the Norwegian Radium Hospital; and Chung Ho-Sun of the University of California, Irvine.
