ArticleScience advances2022
Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug-resistant gliomas.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 0 citations in OpenAlex.
- Deacetylase-independent HDAC1 condensation defines temozolomide response in glioblastoma.Nature chemical biology · 2026Article
- Real-time search-assisted multiplexed quantitative proteomics reveals system-wide cryptic translation initiation in human cancer cells.Genome biology · 2026Article
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Cysteine addiction in drug resistant glioblastoma and therapeutic targeting with designer selenium compounds.Neuro-oncology · 2026Article
- Metal-based nanomaterials achieve tumor treatment strategies by overcoming the blood-brain barrier of glioma and responding to the tumor microenvironment.Materials today. Bio · 2026Review
- Artificial Intelligence-Based In Silico Evaluation of the Pharmacological Potential and In Vitro Anti-Malignancy Effect in the Human Glioblastoma Cell Line of the Hydrate of the Coumarin Compound Meranzin Originating From the Edible Macroalga (Food science & nutrition · 2026Article
- Role of elevation of glycolysis in tumor-associated macrophages in glioblastoma immune evasion and therapeutic implications.PNAS nexus · 2026Review
- Isorhamnetin from Astragalus membranaceus exerts anti-glioma effects via PI3K/Akt signaling pathway.American journal of cancer research · 2026Article
- Review
- G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer cells.Genome biology · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- A single-cell transcriptomic atlas of immune cells in Wilson disease identifies copper-specific immune regulation.iScience · 2025Article
- Oxidative stress induced protein aggregation via GGCT produced pyroglutamic acid in drug resistant glioblastoma.iScience · 2025Article
- The emerging roles of aberrant alternative splicing in glioma.Cell death discovery · 2025Review
- The function of TRIML2 on the temozolomide resistance in glioblastoma.Annals of medicine and surgery (2012) · 2025Article
- RNA G-quadruplexes and stress: emerging mechanisms and functions.Trends in cell biology · 2024Review
- CDK7 and CDK9 inhibition interferes with transcription, translation, and stemness, and induces cytotoxicity in GBM irrespective of temozolomide sensitivity.Neuro-oncology · 2024Article
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
- Article
- Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling.Journal of nanobiotechnology · 2023Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Temozolomide (TMZ) is a chemotherapeutic agent that has been the first-line standard of care for the aggressive brain cancer glioblastoma (GBM) since 2005. Although initially beneficial, TMZ resistance is universal and second-line interventions are an unmet clinical need. Here, we took advantage of the known mechanism of action of TMZ to target guanines (G) and investigated G-rich G-quadruplex (G4) and splice site changes that occur upon TMZ resistance. We report that TMZ-resistant GBM has guanine mutations that disrupt the G-rich DNA G4s and splice sites that lead to deregulated alternative splicing. These alterations create vulnerabilities, which are selectively targeted by either the G4-stabilizing drug TMPyP4 or a novel splicing kinase inhibitor of cdc2-like kinase. Last, we show that the G4 and RNA binding protein EWSR1 aggregates in the cytoplasm in TMZ-resistant GBM cells and patient samples. Together, our findings provide insight into targetable vulnerabilities of TMZ-resistant GBM and present cytoplasmic EWSR1 as a putative biomarker.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.