{
  "abstract": "Obesity has an adverse effect on survival of women with ovarian cancer (OC), supporting a link between obesity, metastatic progression, and therapeutic response, but comprehensive mechanistic insight is lacking. In pre-clinical models of diet-induced obesity and OC, mice fed a high fat diet (HFD) exhibit substantially increased tumor burden relative to low fat diet (LFD) mice and respond poorly to standard-of-care (SOC) chemotherapy. Both HFD murine tumors and tumors from women with BMI>30 show increased expression and nuclear localization of sterol regulatory element binding protein 1 (SREBP1), a master regulator of lipogenesis and lipid transport. The objective of this study was to assess whether inhibition of SREBP1 processing could improve SOC chemotherapy response in obesity-associated OC. We evaluated the FDA-approved drug Nelfinavir (NFV), a pharmacologic inhibitor of site-2 protease that blocks SREBP1 processing, in combination with SOC (paclitaxel+carboplatin) chemotherapy in preclinical models of diet-induced obesity and OC. Our results demonstrate significantly improved therapeutic response, corresponding changes in intra-tumoral adipocytes, and reprogramming of the obesity-driven ascites immune microenvironment. These findings support a model in which NFV-mediated inhibition of SREBP1 processing disrupts obesity-associated metabolic pathways linked to immune suppression and therapeutic resistance, thereby enhancing response to SOC chemotherapy in obesity-associated OC. Collectively, these results highlight metabolic targeting as a strategy to improve therapeutic outcomes in obesity-associated ovarian cancer.",
  "abstract_shown": true,
  "affiliations": [
    "UNIVERSITY OF NOTRE DAME"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "J. Yang"
    },
    {
      "name": "T. S. HILLIARD"
    },
    {
      "name": "Y. LIU"
    },
    {
      "name": "E. RICHARDSON"
    },
    {
      "name": "S. SANTOSO"
    },
    {
      "name": "V. KHOMENKO"
    },
    {
      "name": "M. CONROY"
    },
    {
      "name": "B. MARTIN"
    },
    {
      "name": "E. CRONBERGER"
    },
    {
      "name": "G. DOMINIQUE"
    },
    {
      "name": "Z. WANG"
    },
    {
      "name": "J. JOHNSON"
    },
    {
      "name": "W. WANG"
    },
    {
      "name": "I. ASILEBO"
    },
    {
      "affs": [
        0
      ],
      "name": "M. S. Stack"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/asdxsvhc2pr92.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.751517",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751517v1.full",
  "id": "asdxsvhc2pr92",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751517v1",
  "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",
      "1306|Cancer, Lipids, and Metabolism"
    ]
  ],
  "openalex": "W7213414527",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751517v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/asdxsvhc2pr92.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:41Z",
      "native_id": "10.64898/2026.09.14.751517",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751517v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Metabolic Targeting of SREBP1 Reprograms the Obesity-Driven Ascites Immune Microenvironment and Enhances Chemotherapy Response in Obesity-Associated Ovarian Cancer",
  "title_text": "Metabolic Targeting of SREBP1 Reprograms the Obesity-Driven Ascites Immune Microenvironment and Enhances Chemotherapy Response in Obesity-Associated Ovarian Cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:41Z",
  "url": "https://research.draconitic.com/paper/asdxsvhc2pr92",
  "venue": "bioRxiv",
  "versions": []
}