{
  "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is characterized by a nutrient-poor, hypoxic, and highly desmoplastic microenvironment that imposes substantial metabolic stress on malignant cells. Under these unfavorable conditions, lipid metabolism reprogramming provides cancer cells with the flexibility needed to maintain growth and survive therapeutic stress. Recent advances have uncovered new links between lipid metabolic reprogramming, the tumor microenvironment, and therapeutic resistance in PDAC, highlighting the need for an updated synthesis of this rapidly evolving field. In this review, we focus on the major tumor-intrinsic alterations in fatty acid and cholesterol–mevalonate metabolism, including changes in lipid synthesis, uptake, desaturation, storage, and oxidative utilization. These processes support membrane homeostasis, oncogenic signaling, and redox control, thereby linking lipid handling directly to tumor progression and treatment adaptation. We further review how these pathways are reshaped by the tumor microenvironment, where cancer-associated fibroblasts, immune cells, adipocytes, and neural-associated cells influence lipid availability, trafficking, and signaling. These reciprocal interactions can shape stromal plasticity, immune suppression, invasion, metastasis, and treatment response. We also evaluate current strategies targeting lipid metabolism and discuss why their clinical translation remains limited by metabolic compensation, tumor heterogeneity, drug specificity, and systemic toxicity. Overall, the available evidence suggests that lipid metabolism in PDAC is better understood as a dynamic, interconnected adaptive network rather than a set of isolated metabolic pathways. This perspective supports biomarker-guided combination strategies that target context-dependent lipid dependencies and treatment-induced metabolic adaptation, rather than relying on inhibition of a single pathway.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University",
    "The First Hospital of Jilin University",
    "Department of Colorectal & Anal Surgery, General Surgery Center, The First Hospital of Jilin University",
    "Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center",
    "Jilin University School of Public Health",
    "Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital Singapore",
    "Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore",
    "Division of Surgical Oncology, National University Cancer Institute Singapore (NCIS), National University Health System",
    "National University Digestive Center (NUCD), National University Health System Singapore"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xingyu Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zitong Ye"
    },
    {
      "affs": [
        2
      ],
      "name": "Liuyang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yubo Chi"
    },
    {
      "affs": [
        3
      ],
      "name": "Tongjia Chu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyu Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanxiang Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Haocheng Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Xinyue Yin"
    },
    {
      "affs": [
        0
      ],
      "name": "Jian Zhang"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Alfred Wei Chieh Kow"
    },
    {
      "affs": [
        0
      ],
      "name": "Huan Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/744jx1zppx6w7.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1977031",
  "fulltext_url": null,
  "id": "744jx1zppx6w7",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1977031/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer, Lipids, and Metabolism"
    ]
  ],
  "openalex": "W7223672637",
  "pdf_url": "https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1977031/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/744jx1zppx6w7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1977031",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1977031/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Lipids, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Decoding lipid metabolic reprogramming in pancreatic ductal adenocarcinoma: from tumor–microenvironment crosstalk to therapeutic resistance",
  "title_text": "Decoding lipid metabolic reprogramming in pancreatic ductal adenocarcinoma: from tumor–microenvironment crosstalk to therapeutic resistance",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/744jx1zppx6w7",
  "venue": "Frontiers in Oncology",
  "versions": []
}