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BRIEF RESEARCH REPORT article

Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1488749
This article is part of the Research Topic The Role and Potential Applications of the Microbiota in Pancreatic Ductal Adenocarcinoma View all articles

Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer

Provisionally accepted
Peder R Braadland Peder R Braadland 1Ingvild Farnes Ingvild Farnes 1Elin H Kure Elin H Kure 1Sheraz Yaqub Sheraz Yaqub 1Adrian Mccann Adrian Mccann 2Per M Ueland Per M Ueland 2Knut Jørgen Labori Knut Jørgen Labori 1Johannes R Hov Johannes R Hov 1*
  • 1 Oslo University Hospital, Oslo, Norway
  • 2 Bevital (Norway), Bergen, Hordaland, Norway

The final, formatted version of the article will be published soon.

    Background/Aims: It was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC.We measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC before initiating neoadjuvant chemotherapy. The majority (61%) of the patients were treated with FOLFIRINOX. We used univariable and multivariable Cox proportional hazards regression to estimate the association between pre-treatment 3-IAA and overall survival.The median serum 3-IAA concentration before chemotherapy was 290 (interquartile range 203-417) ng/mL. The unadjusted hazard ratio (HR) for pre-treatment log2(3-IAA) was 0.93, 95% confidence interval (CI) [0.74-1.16], p=0.52. When adjusting for age, ECOG, CA19-9 and tumor classification, the HR for log2(3-IAA) was 0.87, 95% CI [0.68-1.12], p=0.28.Our findings suggest that the potentiating effect of 3-IAA observed in metastatic PDAC undergoing chemotherapy may not translate to borderline resectable or locally advanced PDAC. We recommend additional clinical validation of 3-IAA's predictive value in different categories of PDAC before implementation attempts in human studies are initiated.

    Keywords: Pancreatic adenocarcinoma, chemotherapy - oncology, biomarkers, microbiome, Indoles

    Received: 30 Aug 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Braadland, Farnes, Kure, Yaqub, Mccann, Ueland, Labori and Hov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Johannes R Hov, Oslo University Hospital, Oslo, Norway

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