{
  "abstract": "Purpose of review\n\nPancreatic ductal adenocarcinoma remains among the deadliest malignancies worldwide, and effective therapies are still lacking. Actinomycetota are among the richest microbial sources of bioactive secondary metabolites, and three agents in clinical use against pancreatic malignancy derive from them - streptozotocin, everolimus and doxorubicin - though all three are indicated for neuroendocrine rather than ductal tumors. This review provides a critical narrative synthesis of Actinomycetota-derived metabolites evaluated in pancreatic cancer models, with every potency value re-derived from the primary literature and interpreted alongside assay conditions and available mechanistic and in vivo evidence.Recent findings\n\nFifty-two compounds from 25 primary reports encompass polyketides, nonribosomal peptides, depsipeptides, RiPPs, alkaloids, ionophores and hybrid scaffolds. Rather than a simple ranking of increasingly potent cytotoxins, the literature poses a sharper question about selectivity. Two compounds are conditionally active: kigamicin D only under nutrient deprivation and BE-43547A₂ only under hypoxia, exploiting the metabolic state that defines the disease rather than any intrinsic difference between malignant and normal cells. Both were recovered by screens built to detect that behavior, and neither has been shown to hold a therapeutic window in vivo. Separately, thiogochangamide B retains activity in gemcitabine-resistant models, while trienomycin A binds STAT3 directly, suppresses proliferation across eight pancreatic lines, achieves 84-98% tumor growth inhibition in xenografts at doses producing no detectable toxicity, and distributes preferentially to pancreatic tissue. Conditional activity is best read as a hypothesis about how such compounds should be sought rather than as an established route to selectivity. Despite remarkable chemical diversity, translation remains constrained by the limited use of normal-cell controls, predictive biomarkers and clinically relevant preclinical models. Screens conducted in nutrient-replete, normoxic monolayer culture will systematically miss compounds of this kind. Future efforts should prioritize compounds that exploit the metabolic liabilities of pancreatic cancer rather than pursuing greater cytotoxic potency.",
  "abstract_shown": true,
  "affiliations": [
    "Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Universidade Estadual da Paraíba (UEPB), Campina Grande, 58429-500, PB, Brazil.",
    "NuBioCaatinga. Núcleo de Bioprospecção da Caatinga, Universidade Federal do Rio Grande do Norte (UFRN), Santa Cruz, 59200-000, RN, Brazil.",
    "FACISA - Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte (UFRN), Santa Cruz, 59200-000, RN, Brazil.",
    "Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, V6T 1Z3, BC, Canada.",
    "Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba (UFPB), João Pessoa, 58051-900, PB, Brazil.",
    "CiTCoM UMR 8038, Faculté de Santé, Université Paris Cité, Paris, France.",
    "Instituto de Ciências Biológicas e da Saúde (ICBS), Universidade Federal de Alagoas (UFAL), Maceió, 57072-970, AL, Brazil. rodriguesjuniorvalnes@gmail.com.",
    "NuBioCaatinga. Núcleo de Bioprospecção da Caatinga, Universidade Federal do Rio Grande do Norte (UFRN), Santa Cruz, 59200-000, RN, Brazil. samuel.cibulski@ufrn.br.",
    "FACISA - Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte (UFRN), Santa Cruz, 59200-000, RN, Brazil. samuel.cibulski@ufrn.br."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Daynara da Silva Pereira Lima",
      "orcid": "0009-0001-5660-524X"
    },
    {
      "affs": [
        0
      ],
      "name": "Marcelly da Silveira Silva",
      "orcid": "0009-0002-8145-0435"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Moisés da Rocha Soares"
    },
    {
      "affs": [
        3
      ],
      "name": "Lucas Evangelista Lima Terceiro",
      "orcid": "0000-0003-1992-2032"
    },
    {
      "affs": [
        4
      ],
      "name": "Natanael Teles Ramos de Lima",
      "orcid": "0000-0002-3062-7707"
    },
    {
      "affs": [
        4
      ],
      "name": "Genil Dantas de Oliveira",
      "orcid": "0009-0002-8940-1988"
    },
    {
      "affs": [
        5
      ],
      "name": "Thalisson Amorim de Souza",
      "orcid": "0000-0002-6000-8747"
    },
    {
      "affs": [
        6
      ],
      "name": "Valnês Silva Rodrigues-Junior",
      "orcid": "0000-0002-4849-2249"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Samuel Paulo Cibulski",
      "orcid": "0000-0003-0503-8692"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5twhcz35y7gy4.bib",
  "cited_by": 0,
  "doi": "10.1007/s11912-026-01842-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13669104",
  "id": "5twhcz35y7gy4",
  "issns": [
    "1523-3790",
    "1534-6269"
  ],
  "landing_url": "https://europepmc.org/article/MED/42873463",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Microbial Natural Products and Biosynthesis"
    ]
  ],
  "openalex": "W7221779551",
  "pdf_url": "https://europepmc.org/articles/PMC13669104?pdf=render",
  "pmcid": "PMC13669104",
  "pmid": "42873463",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5twhcz35y7gy4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42873463",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42873463"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Microbial Natural Products and Biosynthesis",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Actinomycetota-Derived Metabolites in Pancreatic Cancer: Chemical Diversity, Metabolic Vulnerability, and Translational Barriers.",
  "title_text": "Actinomycetota-Derived Metabolites in Pancreatic Cancer: Chemical Diversity, Metabolic Vulnerability, and Translational Barriers.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/5twhcz35y7gy4",
  "venue": "Current oncology reports",
  "versions": []
}