Childrens HospitalPrograms & Doctors

Dear Members and Supporters of the Bogart Pediatric Cancer Research Program:

We very much appreciate your continued commitment to the Bogart Pediatric Cancer Research Program, which conducts leukemia and cancer research for infants, children, and adolescents.  Your funding is vitally important for our quest to cure children with these diseases.

Investigators in the Pediatric Cancer and Leukemia Program investigate childhood malignancies of the nervous system (brain tumors, neuroblastoma), the eye (retinoblastoma) muscle and bone (sarcomas), and blood cells (leukemias). The following highlights some of our accomplishments in the past year.

Gene Activity Profile Identifies High-Risk Neuroblastoma. Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid tumors in infants and children. Using “gene chips” Drs. Shahab Asgharzadeh and Robert Seeger discovered 55 genes whose (activity) expression can be used to determine the chance of survival for children with widespread (metastatic) disease. This information also likely will lead to the discovery of genes and networks of genes that could be targeted in new therapeutic strategies. Collectively, this research will make it possible to individualize care for each patient based on definition of a tumor’s gene signature.

Normal cells can form blood vessels that help cancers to grow. Cancer cells must survive and grow in their microenvironment in order to become a problem for patients. Drs. Anat Epstein and Yves DeClerck have provided new information about how blood vessels, which are essential for providing nutrients and oxygen to the tumor cells, form. Dr. Epstein found that cells lining blood vessels must have an anchoring foundation in order to survive and maintain blood flow. Dr. DeClerck showed that cells forming a supporting scaffold around these lining cells also are key to maintaining a nutritious blood supply to tumors. Both of these cell types can be targeted therapeutically to disrupt blood supply and thus to cause tumors to stop growing or shrink.

Normal cells can help leukemia cells resist treatment. Drs. John Groffen and Nora Heisterkamp used a model of childhood leukemia that they developed in mice to understand how resistance to the drug imatinib (Gleevec) may develop in patients. They showed that normal cells could protect leukemia cells from being killed by this drug. This is important because it suggests that imatinib may be more effective in children if this effect of normal cells could be blocked.

Integrated research teams continue to thrive. We have used our successful “bench to bedside” translational research strategy for neuroblastoma to continue developing teams of laboratory and clinical investigators who work together. Failure of current therapies for brain tumors and leukemias are among the greatest challenges facing us. Thus, funding from Bogart is providing “seed capital” to establish outstanding groups of laboratory and clinical investigators to tackle these two problems. For example, studies of young children with brain tumors seek to cure them and importantly to also preserve their ability to learn and function in society. Thus, our brain tumor researchers seek to “save lives and save neurons”.

Clinical testing of new treatments. In the area of clinical trials, Bogart physicians test new therapies that are based upon laboratory findings. We have organized multi-institution consortia that specialize in testing new strategies for childhood neuroblastoma (www.nant.org), brain tumors (www.childrensheadstart.org), and leukemia (www.tacl.us). Childrens Hospital Los Angeles is the only institution in the US that leads three clinical trials consortia.

New faculty. Shahab Asgharzadeh, M.D., who is clinically trained in Pediatric Hematology-Oncology, was recruited for his specialized skills in analyzing information from “gene chips” (bioinformatics). Markus Muschen, M.D., Ph.D., who is an outstanding leukemia laboratory investigator will study how leukemia cells become resistant to therapy and develop new treatment strategies. He will lead our development of a leukemia research team. Thomas C. Lee, M.D., who is an ophthalmologist, will perform laboratory investigations aimed at understanding how normal cells promote the growth of retinoblastoma cells in the eye. Araz Marachelian, M.D., Leo Mascarenhas, M.D., and Rima Jubran, M.D. are clinical investigators with expertise in performing clinical studies of neuroblastoma, sarcomas, and retinoblastoma respectively. These recruitments will further strengthen our research program in important areas.

Summary. Many of the advances that we have made and will continue to make are possible because of the consistent support of the Bogart Pediatric Cancer Research Program. Your support has allowed us to retain and recruit some of the best research scientists and clinical investigators. We are proud of our accomplishments, but we are equally proud of your continued commitment to us.

Sincerely yours,

Stuart E. Siegel, M.D.
Director, Pediatric Cancer Research Program
Director, Childrens Center for Cancer and Blood Diseases
Childrens Hospital Los Angeles

Robert C. Seeger, M.D.
Principal Investigator, Pediatric Cancer Research Program
Director, Bogart Memorial Laboratories
Director, Cancer Research Program
Childrens Hospital Los Angeles Research Institute