Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics
IntroductionThe 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 tr...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1513258/full |
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| author | Kee Kiat Yeo Kee Kiat Yeo Joanna Gell Joanna Gell Joanna Gell Girish Dhall Girish Dhall Ching Lau Ching Lau Ching Lau |
| author_facet | Kee Kiat Yeo Kee Kiat Yeo Joanna Gell Joanna Gell Joanna Gell Girish Dhall Girish Dhall Ching Lau Ching Lau Ching Lau |
| author_sort | Kee Kiat Yeo |
| collection | DOAJ |
| description | IntroductionThe 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.MethodsWe 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.ResultsWe discuss the advancements in the understanding of the underlying genetic changes in intracranial GCT and the utility of novel molecular techniques in the diagnosis and classification of intracranial germ cell tumors as well as development of potential novel therapeutics.DiscussionDevelopment of liquid biopsy platforms for diagnosis and management of malignancies is a rapidly growing field. Current approach utilizing traditional tumor markers have significant limitations. In this review, we will discuss profiling of intracranial GCTs for genetic and 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. |
| format | Article |
| id | doaj-art-d26f302f92074341910c9946b4ddd273 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-d26f302f92074341910c9946b4ddd2732025-01-31T06:40:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011510.3389/fonc.2025.15132581513258Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeuticsKee Kiat Yeo0Kee Kiat Yeo1Joanna Gell2Joanna Gell3Joanna Gell4Girish Dhall5Girish Dhall6Ching Lau7Ching Lau8Ching Lau9Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, United StatesDepartment of Pediatrics, Harvard Medical School, Boston, MA, United StatesCenter for Cancer and Blood Disorders, Connecticut Children’s Medical Center, Hartford, CT, United StatesThe Jackson Laboratory for Genomic Medicine, Framingham, CT, United StatesDepartment of Pediatrics, University of Connecticut School of Medicine, Framington, CT, United StatesAlabama Center for Childhood Cancer and Blood Disorders at Children’s of Alabama, Birmingham, AL, United StatesDepartment of Pediatrics, Marnix E. Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesCenter for Cancer and Blood Disorders, Connecticut Children’s Medical Center, Hartford, CT, United StatesThe Jackson Laboratory for Genomic Medicine, Framingham, CT, United StatesDepartment of Pediatrics, University of Connecticut School of Medicine, Framington, CT, United StatesIntroductionThe 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.MethodsWe 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.ResultsWe discuss the advancements in the understanding of the underlying genetic changes in intracranial GCT and the utility of novel molecular techniques in the diagnosis and classification of intracranial germ cell tumors as well as development of potential novel therapeutics.DiscussionDevelopment of liquid biopsy platforms for diagnosis and management of malignancies is a rapidly growing field. Current approach utilizing traditional tumor markers have significant limitations. In this review, we will discuss profiling of intracranial GCTs for genetic and 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1513258/fullgerm cell tumorcentral nervous systemintracranialgenomicsliquid biopsytherapeutics |
| spellingShingle | Kee Kiat Yeo Kee Kiat Yeo Joanna Gell Joanna Gell Joanna Gell Girish Dhall Girish Dhall Ching Lau Ching Lau Ching Lau Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics Frontiers in Oncology germ cell tumor central nervous system intracranial genomics liquid biopsy therapeutics |
| title | Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics |
| title_full | Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics |
| title_fullStr | Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics |
| title_full_unstemmed | Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics |
| title_short | Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics |
| title_sort | intracranial germ cell tumors advancement in genomic diagnostics and the need for novel therapeutics |
| topic | germ cell tumor central nervous system intracranial genomics liquid biopsy therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1513258/full |
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