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Review
. 2023 Sep 13:13:1254645.
doi: 10.3389/fonc.2023.1254645. eCollection 2023.

Bridging the age gap: a review of molecularly informed treatments for glioma in adolescents and young adults

Annette Weiser  1   2 , Astrid Sanchez Bergman  1 , Charbel Machaalani  1 , Julie Bennett  3   4 , Patrick Roth  5 , Regina R Reimann  6 , Javad Nazarian  7   8 , Ana S Guerreiro Stucklin  1   2
Affiliations
Review

Bridging the age gap: a review of molecularly informed treatments for glioma in adolescents and young adults

Annette Weiser et al. Front Oncol. .

Abstract

Gliomas are the most common primary central nervous system (CNS) tumors and a major cause of cancer-related mortality in children (age <15 years), adolescents and young adults (AYA, ages 15-39 years), and adults (age >39 years). Molecular pathology has helped enhance the characterization of these tumors, revealing a heterogeneous and ever more complex group of malignancies. Recent molecular analyses have led to an increased appreciation of common genomic alterations prevalent across all ages. The 2021 World Health Organization (WHO) CNS tumor classification, 5th edition (WHO CNS5) brings forward a nomenclature distinguishing "pediatric-type" and "adult-type" gliomas. The spectrum of gliomas in AYA comprises both "pediatric-like" and "adult-like" tumor entities but remains ill-defined. With fragmentation of clinical management between pediatric and adult centers, AYAs face challenges related to gaps in medical care, lower rates of enrollment in clinical trials and additional psychosocial and economic challenges. This calls for a rethinking of diagnostic and therapeutic approaches, to improve access to appropriate testing and potentially beneficial treatments to patients of all ages.

Keywords: AYA (adolescents and young adults); BRAF; IDH mutation; PI3K-AKT pathway; WHO CNS5; gliomas; histone mutations; targeted therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of glioma-associated molecular alterations across different ages. (Created with BioRender.com).
Figure 2
Figure 2
Main molecular drivers of glioma. (A) Genetic alterations activating the Ras/MAPK pathway, including loss of function mutations in NF1 and gain of function mutations or fusions in BRAF and Receptor Tyrosine Kinases (RTKs); (B) DNA hypomethylation as a result of Polycomb repressive complex 2 (PRC2) inhibition by H3K27M or EZHIP overexpression (mutually exclusive); (C) IDH mutations leading to an accumulation of D-2 hydroxyglutarate and decrease in TET-mediated DNA demethylation. (Created with BioRender.com).
See this image and copyright information in PMC

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