Pediatric high‐grade glioma: moving toward subtype‐specific multimodal therapy. (11th February 2021)

• Record Type: Journal Article
• Authors: Chatwin, Hannah V.; Cruz Cruz, Joselyn; Green, Adam L.
• Is Part Of: FEBS journal. Volume 288:Number 21(2021)
• Page Start: 6127
• Page End: 6141
• Publication Date: 2021-02-11
• Subjects: convection‐enhanced delivery -- immunotherapy -- pediatric high‐grade glioma -- radiation‐induced glioma; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15739
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Pediatric high‐grade gliomas (pHGG) comprise a deadly, heterogenous category of pediatric gliomas with a clear need for more effective treatment options. Advances in high‐throughput molecular techniques have enhanced molecular understanding of these tumors, but outcomes are still poor, and treatments beyond resection and radiation have not yet been clearly established as standard of care. In this review, we first discuss the history of treatment approaches to pHGG to this point. We then review four distinct categories of pHGG, including histone 3‐mutant, IDH‐mutant, histone 3/IDH‐wildtype, and radiation‐induced pHGG. We discuss the molecular understanding of each subgroup and targeted treatment options in development. Finally, we look at the development and current status of two novel approaches to pHGG as a whole: localized convection‐enhanced chemotherapy delivery and immunotherapy, including checkpoint inhibitors, vaccine therapy, and CAR‐T cells. Through this review, we demonstrate the potential for rational, molecularly driven, subtype‐specific therapy to be used with other novel approaches in combinations that could meaningfully improve the prognosis in pHGG. Abstract : Pediatric high‐grade gliomas are aggressive, deadly tumors with limited treatment options. Recent greater molecular understanding of these tumors has created opportunities for targeted, combinatorial therapies capable of making a meaningful impact on survival. Here, we review the current understanding of pediatric high‐grade glioma molecular subtypes, progress in targeted treatment, and novel therapeutic modalities, including immunotherapy and convection‐enhanced delivery of chemotherapy. We discuss how combining existing and novel treatments could significantly improve outcomes for these patients.