The Role of Neurodevelopmental Pathways in Brain Tumors

Over the course of many decades, cancer researchers have sought to define the genetic alterations and common mechanisms by which brain and spinal tumors exert their functions. Continued pursuit of these answers has highlighted parallels that exist between developmental paradigms and tumorigenesis and the contributions of neurodevelopmental pathways to the initiation and continued growth of central nervous system (CNS) tumors. Successful development of the human nervous system depends on a sequence of well-orchestrated molecular signaling events that are tightly regulated over specific periods of time. Genetic and environmental factors are carefully modulated through a series of cellular signaling cascades and in turn direct neurogenesis in the developing embryo. Most neurodevelopmental factors are expressed for determinate periods of time during neurulation and embryonic neurogenesis, and are then inactivated or downregulated following the end of the gestational period. Studies over the past two decades have emerged highlighting a link between dysregulated neurodevelopmental events and the onset of neurological pathologies, including brain tumors, epilepsy, and neurodegenerative diseases. Disruptions in the transcriptomic profiles of cell signaling molecules known to play an essential role in the patterning of the nervous system have been implicated in the initiation, progression, and metastasis of neurological cancers. A better understanding of how abnormal gene expression and aberrant levels of microenvironmental factors contribute to neuropathological development may help better elucidate potential molecular targets for novel therapies. In this review, we will focus on the current literature linking neurodevelopmental signaling events to disorders of the central nervous system (CNS), and will discuss established and prospective therapeutic targets for the treatment of these fatal pediatric and adult diseases.