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An Insight into Pathophysiological Features and Therapeutic Advances on Ependymoma.

ABSTRACT: Glial cells comprise the non-sensory parts of the central nervous system as well as the peripheral nervous system. Glial cells, also known as neuroglia, constitute a significant portion of the mammalian nervous system and can be viewed simply as a matrix of neural cells. Despite being the "Nervenkitt" or "glue of the nerves", they aptly serve multiple roles, including neuron repair, myelin sheath formation, and cerebrospinal fluid circulation. Ependymal cells are one of four kinds of glial cells that exert distinct functions. Tumorigenesis of a glial cell is termed a glioma, and in the case of an ependymal cell, it is called an ependymoma. Among the various gliomas, an ependymoma in children is one of the more challenging brain tumors to cure. Children are afflicted more severely by ependymal tumors than adults. It has appeared from several surveys that ependymoma comprises approximately six to ten percent of all tumors in children. Presently, the surgical removal of the tumor is considered a standard treatment for ependymomas. It has been conspicuously evident that a combination of irradiation therapy and surgery is much more efficacious in treating ependymomas. The main purpose of this review is to present the importance of both a deep understanding and ongoing research into histopathological features and prognoses of ependymomas to ensure that effective diagnostic methods and treatments can be developed.

SUBMITTER: Seo SH

PROVIDER: S-EPMC8269186 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ependymomas are rare glial tumors with clinical and biological heterogeneity, categorized into supratentorial ependymoma, posterior fossa ependymoma, and spinal cord ependymoma, according to anatomical localization. Spinal ependymoma comprises four different types: spinal ependymoma, spinal ependymoma MYCN-amplified, myxopapillary ependymoma, and subependymoma. The clinical onset largely depends on the spinal location of the tumor. Both non-specific and specific sensory and/or motor symptoms can be present. Owing to diverse features and the low incidence of spinal ependymomas, most of the current clinical management is derived from small retrospective studies, particularly in adults. Treatment involves primarily surgical resection, aiming at maximal safe resection. The use of radiotherapy remains controversial and the optimal dose has not been established; it is usually considered after subtotal resection for WHO grade 2 ependymoma and for WHO grade 3 ependymoma regardless of the extent of resection. There are limited systemic treatments available, with limited durable results and modest improvement in progression-free survival. Thus, chemotherapy is usually reserved for recurrent cases where resection and/or radiation is not feasible. Recently, a combination of temozolomide and lapatinib has shown modest results with a median progression-free survival (PFS) of 7.8 months in recurrent spinal ependymomas. Other studies have explored the use of temozolomide, platinum compounds, etoposide, and bevacizumab, but standard treatment options have not yet been defined. New treatment options with targeted treatments and immunotherapy are being investigated. Neurological and supportive care are crucial, even in the early stages. Post-surgical rehabilitation can improve the consequences of surgery and maintain a good quality of life, especially in young patients with long life expectancy. Here, we focus on the diagnosis and treatment recommendations for adults with spinal ependymoma, and discuss recent molecular advances and new treatment perspectives.

Project description:Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.

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An Insight into Pathophysiological Features and Therapeutic Advances on Ependymoma.

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