ArticleCancer research2025
Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Camrelizumab plus nimotuzumab as second-line therapy for advanced esophageal squamous cell carcinoma: a multicenter phase II study.Journal for immunotherapy of cancer · 2026Trial
- Review
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- TNG961 Is a Selective Oral HBS1L Molecular Glue Degrader for the Treatment of FOCAD-Deleted Cancers.Cancer discovery · 2026Article
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- Acquired Resistance to the PRMT5 Inhibitor Confers Collateral Sensitivity to MEK Inhibition inBiomolecules · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Targeting ClassicalCancers · 2026Review
- Immunohistochemical Loss of MTAP as a Diagnostic and Prognostic Surrogate ofDiagnostics (Basel, Switzerland) · 2026Review
- Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.Targeted oncology · 2026Review
- Review
- Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer.bioRxiv : the preprint server for biology · 2026Article
- Gamma-aminobutyric acid transaminase mediates tumor suppression in renal cell carcinoma through the cGAS-STING-interferon-β axis.Scientific reports · 2026Article
- Real-World Prevalence and Structural Validation of the Canonical 9p21 MTAP-CDKN2A/B Deletion in Non-NSCLC Solid Tumors.Cancers · 2026Article
- Therapy-induced mRNA, rRNA and tRNA methylation alterations confer tolerance phenotype in tumor cells: mechanism and implications.International journal of biological sciences · 2026Review
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in MTAP-deleted (MTAP-del) cancers. The MTA-cooperative PRMT5 inhibitor BMS-986504 exhibited potent and selective antitumor activity in MTAP-del preclinical models and demonstrated activity in MTAP-del patients without the toxicity associated with previous PRMT5 inhibitors. In this study, we focused on pancreatic ductal adenocarcinoma (PDAC), ∼22% of which are MTAP-del, and demonstrated that BMS-986504 suppressed PRMT5 function and cell growth in MTAP-del cells and xenograft models. CRISPR/Cas9 loss-of-function screens implicated cotargeting KRAS as a combination strategy. Concurrent inhibition of PRMT5 and KRASG12C/D enhanced and prolonged suppression of PDAC growth. RNA sequencing analysis revealed that PRMT5 inhibition disrupted RNA splicing of genes essential for PDAC growth. Although PRMT5 and KRAS regulated distinct transcriptomes, they converged on pathways governing cancer cell growth and expression of PDAC-essential genes. These findings provide rationale for combined inhibition of PRMT5 and KRAS in MTAP-del/KRAS-mutant PDAC. SIGNIFICANCE: MTAP deletion and mutational activation of KRAS create therapeutic vulnerabilities for MTA-cooperative PRMT5 and mutant-selective KRAS inhibitors, respectively, providing the rationale for their combination therapy for MTAP-deleted, KRAS-mutant pancreatic cancer. See related article by Knoll et al., p. 3518.
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