Ependymoma in children: Current treatment strategies and evolving molecular biology

Ependymomas are the third commonest tumor of the central nervous system (CNS) accounting for 6-12% of brain tumors in children. Even with advances in neurosurgical, neuroimaging and postoperative adjuvant therapy, the prognosis remains poor with a 5 year progression free survival (PFS) of 23-45%. Recurrence of tumor develops in 50% of cases, even after complete surgical resection followed by radiotherapy. To-date no chemotherapeutic regimen has proven to be of significant clinical benefit. Predicting tumor behavior and defining robust correlates of disease outcome based on histopathology and clinical characteristics remains suboptimal. Paucity of cell lines, failure to develop animal models of these tumors unlike other CNS malignancies, has precluded better understanding of the oncogenic drivers, undermining development of targeted therapy. Thus these tumors have remained therapeutically frustrating and enigmatic. However, over the last few years major breakthrough in the understanding of the molecular biology and subtypes, cellular origin of these tumor cells and signaling pathways are now providing insights into development of biological targeted therapies in ependymoma. It is now clear that even with histopathological similarities, these are genetically heterogeneous tumors with diverse clinical outcomes. Rapid evolution of data now suggests three principal molecular subgroups of ependymomas in children, based on gene clustering. These include supratentorial (ST), posterior fossa (PF) and the spinal (SP) and posterior fossa (PF) subtypes. More recently based on transcriptome profiling, two subgroups (Group A and B) of PF ependymomas have been identified with distinct molecular, clinical characteristics and specific chromosomal aberrations. Signaling pathways specific to these subtypes have now been delineated, raising hopes of defining therapeutic targets. In the years ahead sustained research endeavors are needed to enhance our understanding of the elusive biology of these tumors. This will enable us to profile optimal biologically driven targeted therapy in addition to conventional treatment modalities to improve survival rate.