Solid tumors in the central nervous system represent the third largest cause of cancer related deaths in the 20 to 35 age group and primary intracranial tumors are the most type of solid tumor in children. The genotoxic agents used in conventional therapy can cause severe side effects and damage, particularly to the developing brain. We are analyzing the role of apoptosis in tumor cell killing to evaluate the potential use of apoptosis-associated genes in therapy for CNS tumors. We have analyzed medulloblastoma cell lines and determined that radiation sensitivity is a function of p53 expression levels and the p53-dependent induction of apoptosis. The introduction of p53 protein into tumor cells lacking functional p53 increased radiation sensitivity by initiating apoptosis and was toxic to these cells. We are currently investigating recurrent PNET for loss of functional p53, the transient delivery of p53 to tumors cells as a means of reducing the effective therapeutic dose of radiation and/or to initiate an effective therapy for recurrent tumors or those that refractive to conventional therapy.
