Neurotrophin Signaling in Medulloblastoma

SIMPLE SUMMARY: Neurotrophins are a family of proteins known for regulating nervous system development and neuronal survival and plasticity. These proteins act by activating specific receptor proteins on the cell surface. More recently, neurotrophins and their receptors emerged as mechanisms contributing to cancer progression. Cancer is the most common cause of disease-related death in children. Here, we review the evidence indicating a role for neurotrophin-mediated cell signaling in medulloblastoma, the most common type of malignant brain cancer of the childhood. In addition, by analyzing gene transcript profiles in datasets of tumors from patients with medulloblastoma, we revealed novel findings supporting neurotrophin receptors as potential molecular prognostic markers of patient survival. ABSTRACT: Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children. We discuss the potential of neurotrophin receptors as new therapeutic targets for the treatment of MB. Overall, activation of TrkA and TrkC types of receptors seem to promote cell death, whereas TrkB might stimulate MB growth, and TrkB inhibition displays antitumor effects. Importantly, we show analyses of the gene expression profile of neurotrophins and their receptors in MB primary tumors, which indicate, among other findings, that higher levels of NTRK1 or NTRK2 are associated with reduced overall survival (OS) of patients with SHH MB tumors.