DFMO-based combination therapy for the treatment of advanced stage neuroblastoma.
Neuroblastoma is a pediatric cancer that doctors have a difficult time identifying. This delay allows the cancer to progress into the advanced stages of the disease when the tumor cells begin to spread throughout the child's body to other organs. At this late stage of tumor development, it is a challenge to find the most effective treatment for this cancer. In addition, if children are diagnosed past the age of two years, the predicted outcome is poor and the current treatment strategies have proven to have little or no effect on the growth and spread of the cancer cells. The advanced stage of Neuroblastoma and a poor predicted outcome is often associated with an abnormally high number of a particular gene that is the code that cells use to make a protein called MYCN. This MYCN protein performs a number of different functions that result in increased proliferation, growth and survival of cancer cells. One of these functions includes increasing the production of amino acid derived compounds called polyamines. These polyamines play a direct role in promoting proliferation, growth and survival of cancer cells. Therefore, I will be examining a combination of inhibitors that will effectively decrease polyamine levels in cancer cells, and also reduce the survival of the cancer cells. This treatment strategy allows the use of low concentrations of these inhibitors to minimize or abolish potential side effects. Therefore, this study could lead to a new and potentially more effective chemotherapeutic treatment for children with advanced Neuroblastoma.