Plant Compound Seen as Possible Brain Tumor Therapy
By Merritt McKinney
NEW YORK (Reuters Health) - Blocking a molecular pathway that goes awry in the most common form of childhood brain cancer may hold promise as a therapy for the disease, new research suggests.
The approach, aimed at tumors called medullablastomas, has not been tested in children yet. But the new study shows that a plant-derived compound that interferes with abnormal growth signals can slow tumor growth in mice and kill medulloblastoma cells taken from human patients.
Depending on the stage of the cancer at diagnosis, 50% to 70% of children survive medulloblastoma, according to the study's lead author, Dr. Philip A. Beachy of Johns Hopkins University and the Howard Hughes Medical Institute in Baltimore, Maryland. But the radiation used to destroy cancer cells that might linger afterward "can cause fairly significant brain damage," he told Reuters Health in an interview.
"An agent that would specifically target the tumor would be great to have," he said.
In previous research, Beachy and his colleagues discovered that the molecular pathway involving a protein called Hedgehog behaves abnormally in children with medulloblastoma. As an embryo forms, the Hedgehog pathway is activated to send signals that guide the appropriate development of other cells. But if the pathway is activated inappropriately later in life, certain cancers may develop, Beachy explained.
Both medulloblastoma and basal cell carcinoma, a common form of skin cancer, have been linked to abnormal activation of the Hedgehog pathway, according to the Johns Hopkins researcher.
In the mid-1990s, Beachy and his colleagues found that cyclopamine, a chemical derived from corn lilies that grow in mountain meadows in the western US, blocks the Hedgehog pathway. So they decided to test it as a treatment for medulloblastoma.
In experiments with a mouse model of medulloblastoma, cyclopamine reduced the growth of cancer cells in the laboratory and shrank tumors implanted in mice. What's more, treatment with the plant chemical killed up to 99.9% of cancer cells in medulloblastoma tumors that had been surgically removed from human patients.
A report on the findings is published in the August 30th issue of Science.
The study "shows the potential for cyclopamine and other drugs that could block the pathway," according to Beachy. The chemical did not cause any side effects in the mice, but it has never been tested in humans, he said.
Still, Beachy said that there is enough evidence of the beneficial effects of cyclopamine to justify developing the chemical so that its safety and effectiveness can be tested in human trials.
It is still uncertain, though, he noted, how much of the chemical can be collected by harvesting corn lilies. Due to the complexity of the chemical, it would be very difficult to make synthetically, according to Beachy.
Financial support for the research was provided by several sources, including Immunex and Curis, Inc. Johns Hopkins holds a financial interest in Curis and is entitled to a share of the royalties that might arise from products related to the research.
SOURCE: Science 2002;297:1559-1561. |
