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MINI REVIEW article

Front. Oncol.
Sec. Pediatric Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1513258
This article is part of the Research Topic Recent Biological Insights into Pediatric Brain Tumors View all 7 articles

Intracranial Germ Cell Tumors: Advancement in Genomic Diagnostics and the need for Novel Therapeutics

Provisionally accepted
Kee Kiat Yeo Kee Kiat Yeo 1,2*Joanna Gell Joanna Gell 3,4,5Girish Dhall Girish Dhall 6,7Ching Lau Ching Lau 3,4,5
  • 1 Harvard Medical School, Boston, Massachusetts, United States
  • 2 Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, United States
  • 3 Connecticut Children's Medical Center, Hartford, Connecticut, United States
  • 4 Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States
  • 5 School of Medicine, University of Connecticut, Farmington, Connecticut, United States
  • 6 Children's of Alabama, Birmingham, Alabama, United States
  • 7 Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States

The final, formatted version of the article will be published soon.

    Introduction: The outcomes for patients with intracranial germ cell tumors (GCT) has improved over the past few decades. However, there remains a lack of a consensus on a standard diagnostic and treatment approach of these tumors. The diagnostic work-up of intracranial GCT remains variable, and the treatment for patients with recurrent disease remains challenging. Methods: We review the current approach in the diagnosis and treatment of intracranial GCT. Given the heterogeneity of these tumors, we highlight the challenges and controversy with these conventional approaches. Results: We discuss the advancements in the understanding of intracranial GCT and the utility of novel molecular techniques in the diagnosis and classification of intracranial germ cell tumors as well as the development of novel therapeutics. Discussion: Development of liquid biopsy platforms for diagnosis and management of malignancies is a rapidly growing field. Current approach utilizing traditional tumor markers have significant limitations. We discuss profiling of intracranial GCTs for genetic/epigenetic signatures, which are emerging as promising biomarkers to assist in the diagnosis and management of intracranial GCTs. Various studies have shown that activating mutations in MAPK pathway are common alterations in intracranial GCTs, with KIT expression seen in most germinomas. Development of targeted therapeutics against KIT has led to the prospect of targeted therapy in germinoma. Other treatment modalities being considered for clinical development include immunotherapy and the use of immune checkpoint inhibitors, especially in NGGCT. In this review, we will discuss the potential novel therapeutics and the clinical trials that are currently under development.

    Keywords: Germ cell tumor, Central Nervous System, intracranial, Genomics, liquid biopsy therapeutics

    Received: 18 Oct 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Yeo, Gell, Dhall and Lau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kee Kiat Yeo, Harvard Medical School, Boston, 02115, Massachusetts, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.