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Review

Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications

1
Department of Hematology and Oncology, University Children’s Hospital Tübingen, 72076 Tübingen, Germany
2
Section of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, 72076 Tübingen, Germany
3
Department of Neuropathology, Institute of Pathology, University Hospital Tübingen, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Cells 2024, 13(14), 1215; https://doi.org/10.3390/cells13141215
Submission received: 31 May 2024 / Revised: 17 July 2024 / Accepted: 18 July 2024 / Published: 19 July 2024
(This article belongs to the Special Issue Pathophysiology of Central Nervous System Tumors)

Abstract

Pediatric low-grade gliomas (PLGGs) comprise a heterogeneous set of low-grade glial and glioneuronal tumors, collectively representing the most frequent CNS tumors of childhood and adolescence. Despite excellent overall survival rates, the chronic nature of the disease bears a high risk of long-term disease- and therapy-related morbidity in affected patients. Recent in-depth molecular profiling and studies of the genetic landscape of PLGGs led to the discovery of the paramount role of frequent upregulation of RAS/MAPK and mTOR signaling in tumorigenesis and progression of these tumors. Beyond, the subsequent unveiling of RAS/MAPK-driven oncogene-induced senescence in these tumors may shape the understanding of the molecular mechanisms determining the versatile progression patterns of PLGGs, potentially providing a promising target for novel therapies. Recent in vitro and in vivo studies moreover indicate a strong dependence of PLGG formation and growth on the tumor microenvironment. In this work, we provide an overview of the current understanding of the multilayered cellular mechanisms and clinical factors determining the natural progression patterns and the characteristic biological behavior of these tumors, aiming to provide a foundation for advanced stratification for the management of these tumors within a multimodal treatment approach.
Keywords: pediatric low-grade glioma; pilocytic astrocytoma; RAS/MAPK pathway; oncogene-induced senescence; tumor microenvironment pediatric low-grade glioma; pilocytic astrocytoma; RAS/MAPK pathway; oncogene-induced senescence; tumor microenvironment
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MDPI and ACS Style

Gorodezki, D.; Schuhmann, M.U.; Ebinger, M.; Schittenhelm, J. Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications. Cells 2024, 13, 1215. https://doi.org/10.3390/cells13141215

AMA Style

Gorodezki D, Schuhmann MU, Ebinger M, Schittenhelm J. Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications. Cells. 2024; 13(14):1215. https://doi.org/10.3390/cells13141215

Chicago/Turabian Style

Gorodezki, David, Martin U. Schuhmann, Martin Ebinger, and Jens Schittenhelm. 2024. "Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications" Cells 13, no. 14: 1215. https://doi.org/10.3390/cells13141215

APA Style

Gorodezki, D., Schuhmann, M. U., Ebinger, M., & Schittenhelm, J. (2024). Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications. Cells, 13(14), 1215. https://doi.org/10.3390/cells13141215

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