ArticleNature communications2021
Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.Cancer discovery · 2023Trial
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- MTAP loss in gastrointestinal cancers is associated with CDKN2A deletion, poor prognosis in gastric carcinoma, and potential relevance for PRMT5-targeted therapy.Scientific reports · 2026Article
- Targeting methionine-induced pyroptosis enhances anti-tumor immunity.Science China. Life sciences · 2026Article
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
- MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.Cells · 2025Review
- A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells.Nature communications · 2025Article
- Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.Cancer research · 2025Article
- Exploiting Synthetic Lethality of PRMT5 for Precision Treatment of MTAP-Deficient Glioblastoma.International journal of translational medicine (Basel, Switzerland) · 2025Article
- Challenging CDKN2A assessment in BRAF-altered gliomas: lessons from a pleomorphic xanthoastrocytoma-enriched cohort.Acta neuropathologica communications · 2025Article
- Article
- Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma.Cell reports. Medicine · 2025Article
- TNG908 is a brain-penetrant, MTA-cooperative PRMT5 inhibitor developed for the treatment of MTAP-deleted cancers.Translational oncology · 2025Article
- MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.Nature communications · 2025Article
- Emerging roles for methionine metabolism in immune cell fate and function.Frontiers in immunology · 2025Review
- A review of the known MTA-cooperative PRMT5 inhibitors.RSC advances · 2024Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP's substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion.
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Registered trials
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.