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- Title
The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses.
- Authors
Ramsoomair, Christian K.; Ceccarelli, Michele; Heiss, John D.; Shah, Ashish H.
- Abstract
Glioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM. Key points: In vivo studies link epitranscriptomic dysregulation with glioma pathogenesis. TCGA shows elevated regulator expression is associated with increased mortality in GBM patients. RNA modifications negatively correlate with GBM immunogenicity and thus reduce the efficacy of immunotherapies in GBM patients. RNA modification regulators represent promising therapeutic agents for reducing mortality and immunotherapy adjuvants for enhancing tumor immunogenicity.
- Subjects
ENDOGENOUS retroviruses; GLIOMAS; TUMOR microenvironment; RNA modification &; restriction; INTRACRANIAL tumors; BRAIN tumors
- Publication
Journal of Translational Medicine, 2023, Vol 21, Issue 1, p1
- ISSN
1479-5876
- Publication type
Article
- DOI
10.1186/s12967-023-04725-z