|Dr. Linda Baum|
Researchers at UCLA’s Jonsson Comprehensive Cancer Center have discovered the mechanism by which an experimental drug, GCS-100, removes a protein from lymphoma cells that prevents the cells from responding to chemotherapy.
This discovery revives hope in GCS-100, a drug that had begun in clinical trials years before but had been delayed indefinitely. The researchers hope GCS-100 can be combined with chemotherapy to create an effective treatment for diffuse large B cell lymphoma (DLBCL), the most common and aggressive form of non-Hodgkin lymphoma, a cancer of the immune system.
The study, posted online ahead of publication in the journal Blood, found that a protein called galectin-3 binds to an enzyme called CD45 on the surface of a lymphoma cell. This protein-enzyme combination regulates susceptibility of the cell to chemotherapy drugs, essentially protecting the cancer cell from chemotherapy.
Derived from citrus pectin, GCS-100 works outside the cell to remove the protective galectin-3. Once the galectin-3 is removed, a lymphoma cell can be effectively killed by chemotherapy drugs, part of a chain-reaction of programmed cancer cell death called apoptosis.
Although they knew the drug had shown action against lymphoma cells, the finding that GCS-100 literally removed the barrier to the initiation of cell death by removing galectin-3 from the lymphoma cell surface was unexpected.
“We let the results guide our ideas, and we were able to establish a mechanism for GCS-100,” said the study’s first author Mary Clark. “I am excited to follow the progress of GCS-100 and hope to see its use in the clinic as an adjunct therapy for lymphoma in the near future.”
Dr. Linda Baum, senior researcher on the study, said, “This drug had been abandoned because of the vagaries of the economy. My hope would be to restart this drug in clinical trials, and using this new knowledge to include it in a more targeted lymphoma therapy.”
Early clinical trials of GCS-100 had shown no known side effects of the drug other than a mild rash in some patients, which other research has shown is the result of the drug also promoting the development of T cells, which are created by the immune system to fight disease.
Funding for this research was provided by the Ron and Maddie Katz Family Foundation and the National Institutes of Health.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2012, the Jonsson Cancer Center was once again named among the nation’s top 10 cancer centers by U.S. News & World Report, a ranking it has held for 12 of the last 13 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.