IDH-mutant gliomas in children and adolescents - from biology to clinical trials
Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors as...
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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.2024.1515538/full |
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| author | Louise Evans Sarah Trinder Sarah Trinder Andrew Dodgshun Andrew Dodgshun David D. Eisenstat David D. Eisenstat David D. Eisenstat James R. Whittle James R. Whittle James R. Whittle Jordan R. Hansford Jordan R. Hansford Jordan R. Hansford Santosh Valvi Santosh Valvi Santosh Valvi |
| author_facet | Louise Evans Sarah Trinder Sarah Trinder Andrew Dodgshun Andrew Dodgshun David D. Eisenstat David D. Eisenstat David D. Eisenstat James R. Whittle James R. Whittle James R. Whittle Jordan R. Hansford Jordan R. Hansford Jordan R. Hansford Santosh Valvi Santosh Valvi Santosh Valvi |
| author_sort | Louise Evans |
| collection | DOAJ |
| description | Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (IDH), with mutated IDH (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors. Despite their rarity, IDH mutations have been reported in 5-15% of pediatric glioma cases. Those with primary mismatch-repair deficient mIDH astrocytomas (PMMRDIA) have a particularly poor prognosis. Here, we describe the biology of mIDH gliomas and review the literature regarding the emergence of mIDH inhibitors, including clinical trials in adults. Given the paucity of clinical trial data from pediatric patients with mIDH glioma, we propose guidelines for the inclusion of pediatric and AYA patients with gliomas onto prospective trials and expanded access programs as well as the potential of combined mIDH inhibition and immunotherapy in the treatment of patients with PMMRDIA at high risk of progression. |
| format | Article |
| id | doaj-art-6f527ed003bc4cd4828fa9970c44aa96 |
| 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-6f527ed003bc4cd4828fa9970c44aa962025-01-28T12:46:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15155381515538IDH-mutant gliomas in children and adolescents - from biology to clinical trialsLouise Evans0Sarah Trinder1Sarah Trinder2Andrew Dodgshun3Andrew Dodgshun4David D. Eisenstat5David D. Eisenstat6David D. Eisenstat7James R. Whittle8James R. Whittle9James R. Whittle10Jordan R. Hansford11Jordan R. Hansford12Jordan R. Hansford13Santosh Valvi14Santosh Valvi15Santosh Valvi16Michael Rice Centre for Hematology and Oncology, Women’s and Children’s Hospital, North Adelaide, SA, AustraliaKids Cancer Centre, Sydney Children’s Hospital, Sydney, NSW, AustraliaChildren’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, Sydney, NSW, AustraliaDepartment of Pediatrics, University of Otago, Christchurch, New ZealandChildren’s Hematology/Oncology Centre, Christchurch Hospital, Christchurch, New ZealandChildren’s Cancer Centre, Royal Children’s Hospital, Melbourne, VIC, AustraliaDepartment of Stem Cell Medicine, Murdoch Children’s Research Institute, Melbourne, VIC, AustraliaDepartment of Pediatrics, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia0Personalized Oncology Division, Walter and Eliza Hall Institute (WEHI), Parkville, VIC, Australia1Department of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaMichael Rice Centre for Hematology and Oncology, Women’s and Children’s Hospital, North Adelaide, SA, Australia2Pediatric Neuro-Oncology, Precision Cancer Medicine, South Australia Health and Medical Reseach Institute, Adelaide, SA, Australia3South Australia ImmunoGENomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia4Department of Pediatric and Adolescent Oncology/Hematology, Perth Children’s Hospital, Nedlands, WA, Australia5Brain Tumor Research Program, Telethon Kids Institute, Nedlands, WA, Australia6School of Medicine, Division of Pediatrics, The University of Western Australia, Perth, WA, AustraliaGliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (IDH), with mutated IDH (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors. Despite their rarity, IDH mutations have been reported in 5-15% of pediatric glioma cases. Those with primary mismatch-repair deficient mIDH astrocytomas (PMMRDIA) have a particularly poor prognosis. Here, we describe the biology of mIDH gliomas and review the literature regarding the emergence of mIDH inhibitors, including clinical trials in adults. Given the paucity of clinical trial data from pediatric patients with mIDH glioma, we propose guidelines for the inclusion of pediatric and AYA patients with gliomas onto prospective trials and expanded access programs as well as the potential of combined mIDH inhibition and immunotherapy in the treatment of patients with PMMRDIA at high risk of progression.https://www.frontiersin.org/articles/10.3389/fonc.2024.1515538/fullIDH mutationlow grade gliomapediatricadolescent and young adultAYA |
| spellingShingle | Louise Evans Sarah Trinder Sarah Trinder Andrew Dodgshun Andrew Dodgshun David D. Eisenstat David D. Eisenstat David D. Eisenstat James R. Whittle James R. Whittle James R. Whittle Jordan R. Hansford Jordan R. Hansford Jordan R. Hansford Santosh Valvi Santosh Valvi Santosh Valvi IDH-mutant gliomas in children and adolescents - from biology to clinical trials Frontiers in Oncology IDH mutation low grade glioma pediatric adolescent and young adult AYA |
| title | IDH-mutant gliomas in children and adolescents - from biology to clinical trials |
| title_full | IDH-mutant gliomas in children and adolescents - from biology to clinical trials |
| title_fullStr | IDH-mutant gliomas in children and adolescents - from biology to clinical trials |
| title_full_unstemmed | IDH-mutant gliomas in children and adolescents - from biology to clinical trials |
| title_short | IDH-mutant gliomas in children and adolescents - from biology to clinical trials |
| title_sort | idh mutant gliomas in children and adolescents from biology to clinical trials |
| topic | IDH mutation low grade glioma pediatric adolescent and young adult AYA |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1515538/full |
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