In children, brain tumors are the most frequent solid cancer and also are the most common cause of cancer-related death. About 3,100 children younger than 20 years are diagnosed each year. Our laboratory research aims to learn more about childhood brain tumors and to develop new treatment strategies.
Medulloblastoma is one of the most common brain tumors of childhood. Studies performed by the Children’s Oncology Group have shown that including radiation therapy in the treatment causes a significant loss of intellectual capacity for survivors. The pioneering “Head Start” clinical trials, which have been directed by Dr. Jonathan Finlay at Children’s Hospital Los Angeles, aim to avoid radiation therapy by using intensive chemotherapy for patients less than 6 years old. The Head Start studies have shown that a significant portion of children, but not all, can be cured of their disease and maintain their intellectual capacity. The major difference between patients who were cured with chemotherapy alone and those who succumbed to disease undoubtedly lies in the genetic makeup of their tumors. Our initial study of 30 medulloblastomas using “gene chips” suggests that gene expression “molecular signatures”, which are based on the level of expression of 54,000 genes in each tumor, can accurately identify at the time of diagnosis children who will survive with chemotherapy alone. This is a major advance since no other test predicts which patients can be cured without radiation. In this preliminary study, the expression of a gene called forkhead box G1 (FoxG1), which is known to be involved in causing cancer, played the most significant role in identifying chemotherapy-curable from incurable tumors.
Our overall goal is to develop a clinically useable assay based on “gene chip” analysis that can be used for treatment planning for children with medulloblastoma. Our immediate goals are (1) to analyze an additional sixty tumors with “gene chips” to provide the foundation for developing a robust gene based survival classifier; and (2) to assess the predictive value of FoxG1 expression in these same tumors as well as in a larger group of tumors.
Funding of the following budget will allow us to complete the first goal and publish for the first time a gene classifier that predicts which children with medulloblastoma will survive with chemotherapy alone. Achieving this goal will provide a test that will identify children who can be cured without radiation therapy and so who will emerge from their treatment with intact intellectual capabilities. |
