My laboratory has a primary interest in understanding what regulates the growth of medulloblastomas, the most common malignant brain tumors of childhood. Medulloblastomas arise by oncogenic transformation of cerebellar granule cells. Several years ago, we discovered that the tumors express neurotrophins and their receptors, and that the expression of the neurotrophin-3 receptor, TrkC, is correlated with clinical outcome. Patients with tumors expressing high levels of trkC have a more favorable outcome than those with low expression. Our results now indicate that TrkC is more than a prognostic marker. Medulloblastomas undergo apoptosis when grown in vitro in the presence of neurotrophin-3 and apoptosis is highly correlated with TrkC expression in tumor biopsy samples. Moreover, medulloblastomas that have been induced to express TrkC grow more slowly as xenografts in nude mice. Since the majority of medulloblastomas also express the TrkC ligand, we have proposed that tumors with high TrkC expression have a better prognosis because the receptors induce cell death.
Ultimately, we aim to use our understanding of growth regulation in the central and peripheral nervous system to devise new therapies based on molecular mechanisms that underlie disease states. For example, experiments are being planned to test whether neurotrophin-3 can be used as a therapy for medulloblastomas, that may be less toxic than the traditional therapies of radiation and chemotherapy.