Department of Hematology and Oncology, University Children's Hospital Tübingen, 72076 Tübingen, Germany.
Section of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, 72076 Tübingen, Germany.
Cells. 2024 Jul 19;13(14):1215. doi: 10.3390/cells13141215.
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.
儿童低级别胶质瘤（PLGGs）包括一组异质性的低级神经胶质瘤和神经胶质神经元肿瘤，它们共同构成了儿童和青少年中枢神经系统肿瘤中最常见的肿瘤。尽管整体存活率很高，但疾病的慢性性质使受影响患者存在长期疾病和治疗相关发病率的高风险。最近对 PLGGs 的深入分子分析和遗传景观研究发现，RAS/MAPK 和 mTOR 信号的频繁上调在这些肿瘤的发生和进展中起着至关重要的作用。此外，随后揭示了这些肿瘤中 RAS/MAPK 驱动的癌基因诱导衰老，可能会加深对决定 PLGGs 多样进展模式的分子机制的理解，并为新的治疗方法提供有希望的靶点。最近的体外和体内研究还表明，PLGG 的形成和生长强烈依赖于肿瘤微环境。在这项工作中，我们概述了目前对决定这些肿瘤自然进展模式和特征性生物学行为的多层次细胞机制和临床因素的理解，旨在为多模式治疗方法中这些肿瘤的综合管理提供基础。
