ArticleNature communications2024
PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Targeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer.Histology and histopathology · 2026Article
- PRMT5 as a Key Driver of Stemness and Metastatic Potential in Triple-Negative Breast Cancer.Biomolecules · 2026Review
- PRMT5 is Frequently Upregulated and a Potential Therapeutic Target in MTAP-deficient Malignant Peripheral Nerve Sheath Tumors.bioRxiv : the preprint server for biology · 2026Article
- Charting the multilevel molecular response to palbociclib in ER-positive breast cancer.NAR cancer · 2026Article
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer.Cancer research · 2026Article
- Therapeutic advances in HR+/HER2- advanced breast cancer after failure of CDK4/6 inhibitor therapy.Frontiers in oncology · 2026Review
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Targeting the LINC01272-FUS signal axis inhibits the migration and invasion of testicular germ cell tumors.Cancer cell international · 2025Article
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.Nature communications · 2025Article
- Exploiting Synthetic Lethality of PRMT5 for Precision Treatment of MTAP-Deficient Glioblastoma.International journal of translational medicine (Basel, Switzerland) · 2025Article
- PRMT5:MEP50 Are Mediators of Treatment-Induced Neuroendocrine Differentiation in Prostate Cancer.The Prostate · 2025Article
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- PRMT5 Regulates Senescence in Retinal Ganglion Cells by Targeting the Wnt/β-Catenin Signaling Cascade.Investigative ophthalmology & visual science · 2025Article
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Authors and funding
25 authors at 7 institutions in 5 countries.
Funding
Abstract
CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.
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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 Socratic graph.