ArticleProceedings of the National Academy of Sciences of the United States of America2024
A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
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
19 citing papers in PubMed, 21 citations in OpenAlex.
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- CELF1 is a non-canonical eIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs.Nucleic acids research · 2026Article
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Evaluation of the impact of Roclaglamide on MDA-MB-231 human breast adenocarcinoma cells by cell culture and molecular approaches.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation.International journal of molecular sciences · 2025Review
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.Journal of proteome research · 2025Article
- Additional Bioactive Silvestrol Analogs from the Roots ofJournal of natural products · 2025Article
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.bioRxiv : the preprint server for biology · 2024Article
- Protein-RNA interactions mediated by silvestrol-insight into a unique molecular clamp.Nucleic acids research · 2024Article
- Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Amidino-rocaglates (ADRs), a class of synthetic rocaglates, are potent inhibitors of SARS-CoV-2 replication through inhibition of viral protein synthesis.Antiviral research · 2024Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
In this study, we aimed to address the current limitations of therapies for macro-metastatic triple-negative breast cancer (TNBC) and provide a therapeutic lead that overcomes the high degree of heterogeneity associated with this disease. Specifically, we focused on well-documented but clinically underexploited cancer-fueling perturbations in mRNA translation as a potential therapeutic vulnerability. We therefore developed an orally bioavailable rocaglate-based molecule, MG-002, which hinders ribosome recruitment and scanning via unscheduled and non-productive RNA clamping by the eukaryotic translation initiation factor (eIF) 4A RNA helicase. We demonstrate that MG-002 potently inhibits mRNA translation and primary TNBC tumor growth without causing overt toxicity in mice. Importantly, given that metastatic spread is a major cause of mortality in TNBC, we show that MG-002 attenuates metastasis in pre-clinical models. We report on MG-002, a rocaglate that shows superior properties relative to existing eIF4A inhibitors in pre-clinical models. Our study also paves the way for future clinical trials exploring the potential of MG-002 in TNBC and other oncological indications.
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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.