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Potential influence of the microbiome environment in patients with biliary tract cancer and implications for therapy

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Abstract

Biliary tract cancers, including intra- and extra-hepatic cholangiocarcinoma as well as gallbladder cancer, are associated with poor prognosis and the majority of patients present with advanced-stage, non-resectable disease at diagnosis. Biliary tract cancer may develop through an accumulation of genetic and epigenetic alterations and can be influenced by microbial exposure. Furthermore, the liver and biliary tract are exposed to the gastrointestinal microbiome through the gut–liver axis. The availability of next-generation sequencing technology has led to an increase in studies investigating the relationship between microbiota and human disease. In particular, the interplay between the microbiome, the tumour micro-environment and response to systemic therapy is a prospering area of interest. Given the poor outcomes for patients with biliary tract cancer, this emerging field of research, through which new biomarkers may be identified, offers potential as a tool for early diagnosis, prognostication or even as a future therapeutic target. This review summarises the available evidence on the microbiome environment in patients with biliary tract cancer, including a discussion around confounding factors, implications for therapy and proposed future directions.

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Fig. 1: Microbial metabolism of bile acids and the enterohepatic circulation [28,29,30,31].
Fig. 2: Flow diagram describing identification of studies reporting on the microbiome environment in biliary tract cancer.

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Acknowledgements

Not applicable

Funding

Dr. Roseanna C Wheatley is studying for an MD, funded by the Timpson Fellowship. The salary of Dr. Angela Lamarca is in part funded by The Christie Charity and the European Union’s Horizon 2020 Research and Innovation Programme [grant number 825510, ESCALON].

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Authors and Affiliations

  1. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK

    Roseanna C. Wheatley, Angela Lamarca, Richard A. Hubner, Juan W. Valle & Mairéad G. McNamara

  2. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK

    Roseanna C. Wheatley, Angela Lamarca, Richard A. Hubner, Juan W. Valle & Mairéad G. McNamara

  3. Cancer Research UK Manchester Institute Cancer Biomarker Centre, University of Manchester, Alderley Park, UK

    Elaine Kilgour

  4. The Library, The Christie NHS Foundation Trust, Manchester, UK

    Timothy Jacobs

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  1. Roseanna C. Wheatley
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  2. Elaine Kilgour
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  4. Angela Lamarca
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Contributions

RW drafted and revised the paper. EK reviewed and approved the final version of the paper. TJ performed the literature search and reviewed and approved the final version of the paper. AL reviewed and approved the final version of the paper. RAH reviewed and approved the final version of the paper. JWV reviewed and approved the final version of the paper. MMN concept initialisation and review and approval of draft and final version of the paper.

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Correspondence to Mairéad G. McNamara.

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Competing interests

RCW: no competing interests to declare. EK: no competing interests to declare. TJ: no competing interests to declare. AL: received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen, Incyte and AAA; advisory honoraria from EISAI, Nutricia Ipsen, QED and Roche; she is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen; all outside scope of this work. RAH has served on the advisory board for Roche, BMS, Eisai, Celgene, Beigene, Ipsen and BTG. He has received speaker fees from Eisai, Ipsen, Mylan and PrimeOncology, and has received travel and educational support from Bayer, BMS and Roche; all outside of the scope of this work. JWV received honoraria from Agios, AstraZeneca, Baxter, Genoscience Pharma, Hutchison Medipharma, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Mundipharma EDO, Mylan, QED, Servier, Sirtex and Zymeworks; and grants, honoraria and non-financial support from NuCana, all outside of the scope of this work. MMN received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana and Mylan. She has served on advisory boards for Celgene, Ipsen, Sirtex, Baxalta and Incyte; all outside of the scope of this work.

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Wheatley, R.C., Kilgour, E., Jacobs, T. et al. Potential influence of the microbiome environment in patients with biliary tract cancer and implications for therapy. Br J Cancer 126, 693–705 (2022). https://doi.org/10.1038/s41416-021-01583-8

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