The Foundation made a research grant in the amount of $2,000,000 to be paid over ten years.
The promising developments at Duke included research on two combination chemotherapies – one of Temodar (temozolomide) and CPT11 and another of BCNU and CPT11. These chemotherapies were tested on children with brain-stem gliomas in clinical trials that evolved directly from lab studies conducted at Duke. Those studies showed that the combination of these agents were particularly synergistic. Temodar is designed to prevent the replication of rapidly dividing cells, such as those in tumors. It is the first chemotherapy for this type of recurrent glioma to come to market in 20 years.
Temodar is a methylating agent that puts a methyl group on a specific part of DNA, which ultimately leads to cell death. CPT11 has been found in lab studies to enhance the activity of both Temodar and BCNU. CPT11 is an inhibitor of topoisomerase, an enzyme that is critical for DNA replication, and is a derivative of camptothecin, a natural substance found in a tree native to China. BCNU is an alkylating agent that directly attacks DNA by putting a cross link between the two strands, resulting in cell death. Karenitecin was another new chemotherapeutic drug being tested at Duke, in collaboration with Texas Baylor Hospital. Like CPT11, it is camptothecin-based. Karenitecin has been observed to have strong antitumor activity at low concentrations and is designed to have less toxicity and drug resistance than other camptothecins. Unlike typical water-soluble camptothecins, Karenitecin is fat soluble, which scientists believe may give it enhanced power to penetrate tissue. These studies represent a portion of the substantial research and clinical trials on brain tumors that continue to take place at Duke. Duke was also in the midst of identifying a vast number of the genes found in a given type of brain tumor. Researchers were looking to see what genes are present in gliomas that are not found in healthy brain cells. If a gene is unique to a brain tumor, it is being targeted for diagnostic purposes and the development of treatment therapies. Over the years many growth factor molecules for specific cells in the body’s immune system have been identified. Methods for growing antigen-presenting cells (an antigen is a substance that produces an immune response), called dendritic cells, have been developed. As a result of this progress, many vaccine trials for different types of cancer were undertaken. For example, Duke researchers were able to culture and expand dendritic cells from brain tumor patients. These dendritic cells were being exposed in test tubes in the laboratory to a large number of gene products from childhood gliomas. These cells are then analyzed for their ability to activate immune cells. Once dendritic cells have been pulsed with specific tumor-related gene products from childhood gliomas and have been shown to activate immune cells, these pulsed dendritic cells can be reintroduced into patients with brain tumors. These clinical trials were designed to allow determination of the safety and effectiveness of these vaccines. Vaccine and immune approaches are particularly promising, since they carry much less toxicity to the normal brain than existing treatments of chemotherapy and radiation therapy. ”Because of the Foundation’s support and general advances taking place in cancer biology, I feel confident that within my lifetime effective treatment of childhood gliomas will become a reality,” said Dr. Darell Bigner, leader of the Neuro-Oncology Program and deputy director of the Duke Comprehensive Cancer Center. Dr. Henry Friedman, co-director of the Clinical Neuro-Oncology Program at the Brain Tumor Center, concurred. “With the help of the Foundation,” he said, “we can accelerate our progress and move closer to successfully treating and ultimately finding a cure for this disease.”