{"doi":"10.1093/neuonc/noae052","title":"Telomeres in glioma: Maintenance mechanisms to therapeutic potential","abstract":"Telomere maintenance is a hallmark of cancer 1 enabling cells to bypass limits on cell replication to attain an immortal state.The newfound immortality allows tumor cells to sustain oncogene-driven proliferation that would otherwise lead to cell senescence or death.Most gliomas achieve replicative immortality through 1 of 2 mechanisms driven by highly recurrent genetic alterations.Targeting of telomere maintenance mechanisms (TMMs), therefore, may have therapeutic potential for many glioma patients.Therapeutic exploitation of the distinct TMMs requires a comprehensive understanding of the molecular players and genetic background.Therapeutic innovations in targeting telomere maintenance could be applied widely to tumors with the same TMM including IDH mutant and wild-type glioma, meningiomas, medulloblastomas, and ependymomas, among others.The review by Waitkus et al. 2 presents a comprehensive summary of the TMMs found within subtypes of adult and pediatric glioma, an expansion from a 2021 review in Neuro-Oncology. 3The new review covers frequent and infrequent TMMs that are either telomerase-dependent or independent.Prior studies are reassessed in the context of WHO 2021 tumor classifications.For clinical relevance, the discussion covers therapeutic agents in preclinical and clinical development that target TMMs and agents that target collateral vulnerabilities related to each TMM.Telomerase reactivation underlies replicative immortality in roughly ~85% of all human cancers and is prevalent in adult and pediatric gliomas.Waitkus et al. provide a comprehensive, yet succinct summary of the TERT promoter alterations that reactivate expression, including the 2 hotspot mutations and rare but recurring tandem duplications activated by the GABP tetramer, chromosomal rearrangements, and TERT expression associated with hypermethylation of the \"TERT hypermethylated oncology region\" of the promoter.TERT promoter mutations are clonal on a tumor wide scale, suggesting telomerase targeting therapies will bypass hurdles related to intratumor heterogeneity. 4 Telomerase activation is mutually exclusive with the alternative lengthening of telomeres (ALT) that enables replicative immortality in ~10%-15% of cancers and a majority of IDH mutant astrocytoma and sarcomas. 5ALT is strongly associated with","journal":"Neuro-Oncology","year":2024,"id":478513,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":81161,"name":"J Costello","orcid":"0000-0003-3189-584X","position":1,"is_corresponding":false},{"id":569921,"name":"Nicholas Stevers","orcid":"0000-0003-1082-6423","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:06:46.330532Z","pmid":"38466631","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}