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It is well acknowledged that genomic instability\/genetic alterations together with tumor-associated inflammation are so called \u201cenabling hallmarks\u201d as they drive the acquisition of the other traits. The microbiome is a key component of the inflammatory tumor stroma. Pancreatic ductal adenocarcinoma (PDAC) in particular is characterized by a pronounced stromal compartment whose role in the acquisition of malignant properties is well documented. Recent studies indicate massive alterations of the microbiome in PDAC tissues compared to healthy pancreas or precursor lesions. However, the mechanistic role of the PDAC-associated microbiome, its influence on the hallmarks of cancer, and how this relates to PDAC malignancy remain poorly understood. This raises the question of whether the tumor-associated microbiome through its direct influence on PDAC cells, their precursors, and the surrounding non-neoplastic cells promotes the acquisition of other hallmarks that drive PDAC development and progression. This perspective article outlines the current knowledge of the impact of the PDAC-associated microbiome on the hallmarks of cancer in PDAC. These current findings support the altered microbiome as a third enabling hallmark of PDAC and emphasize that further mechanistic studies are urgently needed to further substantiate its fundamental importance for this tumor entity. This knowledge will provide the basis for clinical translation to develop more effective therapeutic approaches for PDAC.<\/jats:p>","DOI":"10.1038\/s41416-025-03324-7","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T17:26:26Z","timestamp":1766251586000},"page":"843-848","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intratumoral microbiome and pancreatic cancer: an enabling hallmark and path to novel treatments?"],"prefix":"10.1038","volume":"134","author":[{"given":"Malte","family":"Carstensen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Marie","family":"Philipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghna","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Niklas","family":"Klenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maxi","family":"Wandmacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6582-0083","authenticated-orcid":false,"given":"Susanne","family":"Sebens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"3324_CR1","doi-asserted-by":"publisher","first-page":"2320280","DOI":"10.1080\/19490976.2024.2320280","volume":"16","author":"MS Cruz","year":"2024","unstructured":"Cruz MS, Tintelnot J, Gagliani N. 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