{
  "abstract": "Triple-negative breast cancer (TNBC) is a clinically challenging disease with limited therapeutic options. MAP kinase-interacting kinases 1 and 2 (MNK1/2)-mediated phosphorylation of eukaryotic initiation factor 4E (eIF4E) promotes oncogenic translation and represents a potential therapeutic target. We previously showed that loss of eIF4E phosphorylation suppresses metastasis but not primary tumor growth. Here, an shRNA screen surveying druggable genes unveiled cyclin-dependent kinase 4 (CDK4) as a genetic vulnerability to MNK1/2 inhibition in MDA-MB-231 TNBC cells. Although CDK4/6 inhibitors are approved for hormone receptor (HR)-positive, HER2-negative breast cancer, they are not approved for TNBC. We demonstrate that MNK1/2 inhibition synergizes with CDK4/6 blockade suppresses TNBC cell growth, a synergy also observed in another independent TNBC cell line (SUM159) using a broader G1/S CDK (CDK2/4/6) inhibitor. Integrated RNA sequencing and ribosome profiling revealed combination-specific changes in translation associated with mitotic checkpoint control and DNA repair. Our findings document MNK1/2 inhibition as a strategy to sensitize TNBC to G1/S CDK inhibition and provide a new avenue for therapeutic combination.",
  "abstract_shown": true,
  "affiliations": [
    "The Rockefeller University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Q. Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Amiri"
    },
    {
      "name": "A. Moshari"
    },
    {
      "name": "B. Diddeniya"
    },
    {
      "name": "P. Akbarnia"
    },
    {
      "name": "A. A. Piric"
    },
    {
      "name": "E. Prando Munhoz"
    },
    {
      "name": "Y. Bagherian"
    },
    {
      "name": "Z. Li"
    },
    {
      "name": "M. A. Bellucci"
    },
    {
      "name": "N. Mahmood"
    },
    {
      "name": "M. Pollak"
    },
    {
      "name": "S. Huang"
    },
    {
      "name": "N. Sonenberg"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/41261nhng0b5f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.750258",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750258v1.full",
  "id": "41261nhng0b5f",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750258v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|PI3K/AKT/mTOR signaling in cancer"
    ]
  ],
  "openalex": "W7213462099",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750258v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/41261nhng0b5f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:45Z",
      "native_id": "10.64898/2026.09.11.750258",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750258v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "A therapeutic vulnerability linking MNK1/2 inhibition and G1/S cyclin-dependent kinase blockade in triple-negative breast cancer",
  "title_text": "A therapeutic vulnerability linking MNK1/2 inhibition and G1/S cyclin-dependent kinase blockade in triple-negative breast cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:45Z",
  "url": "https://research.draconitic.com/paper/41261nhng0b5f",
  "venue": "bioRxiv",
  "versions": []
}