Investigators at the Mayo Clinic, Rochester, MN; George Washington University, and Children’s National Brain Tumor Institute, Washington, DC review the molecular pathways implicated in pediatric brain tumors, biologic agents that target these pathways, and current clinical trials of these novel therapies. Two major classes of newer biological agents include monoclonal antibodies against growth factor ligands or ligand-binding sites and the small molecule inhibitors that target the intracellular tyrosine kinase domains. The overexpression of the epidermal growth factor receptors found in brainstem gliomas, ependymomas, and medulloblastomas make these receptors a rational therapeutic target. Other targets for biological therapy include the platelet-derived growth factor receptor, angiogenesis inhibitors, and the Sonic Hedgehog pathway that plays a role in embryogenesis and is implicated in the pathogenesis of medulloblastoma. Tumors exhibit immune tolerance, and the induction of immunological responses to tumors using tumor vaccines offers a further promising approach to treatment. 
COMMENT. With a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in pathogenesis of brain tumors, clinical trials of novel biologic agents are showing better CNS penetration and lower toxicity profiles compared with conventional chemotherapy. The effects of newer targeted agents on the developing nervous system must be further investigated since the pediatric brain may be more vulnerable to toxicity.