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New Approaches to Neuroblastoma Therapy

Institution: 
Children's Hospital Los Angeles
Researcher(s): 
Robert Seeger
Grant Type: 
Phase I/II Infrastructure Grants
Year Awarded: 
2008
Type of Childhood Cancer: 
Neuroblastoma
Project Description: 
Neuroblastoma is the second most common solid cancer of children, and less than 50% of children survive who have the widespread (metastatic) form of the disease. The New Approaches to Neuroblastoma Therapy (NANT) consortium is a group of 13 university children’s cancer centers that are dedicated to finding new treatments that will cure more patients (see www.nant.org). The aim of our studies is to develop and test new therapeutic strategies that are developed in our laboratories and that may be effective against the most difficult neuroblastomas. The treatment protocols, which are carefully controlled and monitored, establish the highest dose that can be given safely, define side effects, and determine activity against neuroblastoma. Special tests are done to see if the treatments are effective against the cancer and to show what levels of drugs or other agents can be achieved in the patient. Examples of treatments being investigated include the following:
• 131I-MIBG, which provides targeted radiation therapy because it is taken up by neuroblastoma cells much more than by normal cells.
• CEP-701, a drug that targets the TRKB gene, interfering with its stimulation of neuroblastoma cell growth.
• Fenretinide, a drug that increases a fat in neuroblastoma cells called ceramide, which causes them to die.
• Zoledronic acid, a drug that blocks destruction of bones by neuroblastoma cells.
• Bevacizumab, a biologic agent called an antibody, that interferes with blood vessels that nourish tumors.
• Interleukin-12 (IL-12), another biologic agent called a cytokine, that activates components of the immune system against tumor cells as well as normal cells that enhance their growth.
 
Thus, a general theme or our research is to target tumor cells as well as key tumor promoting normal cells that associate with them in the "environment" of the tumor. Our studies will identify new therapeutic strategies that likely will improve survival for children with high-risk neuroblastoma.