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Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation

Abstract

The intersection of the microbiota and cancer and the mechanisms that define these interactions are a fascinating, rapidly evolving area of cancer biology and therapeutics. Here we present recent insights into the mechanisms by which specific bacteria or their communities contribute to carcinogenesis and discuss the bidirectional interplay between microbiota and host gene or epigenome signaling. We conclude with comments on manipulation of the microbiota for the therapeutic benefit of patients with cancer.

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Fig. 1: Community and individual microbiota contributions to carcinogenesis.
Fig. 2: Microbial metabolite-mediated signaling in the colonic epithelium.
Fig. 3: Mechanisms of host–microbiota and tumor gene–microbiota interactions.

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Acknowledgements

We thank all members of the Sears laboratory and our collaborators for their helpful discussions and contributions over time. We also thank the many individuals who have participated in our studies, enabling our work on the human microbiome and CRC. Figures were created with https://biorender.com. For funding, this work was supported by Bloomberg Philanthropies, a Cancer Grand Challenges OPTIMISTICC team grant (A27140) funded by Cancer Research UK (C.L.S.); National Cancer Institute grant K08CA263316-02 (F.S.); the Biocodex Microbiota Foundation, a Pearl M. Stetler award, a Burroughs Wellcome Fund Career Award for Medical Scientists (1022128) and a Black in Cancer award funded by the Emerald Foundation (J.Q.).

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Correspondence to Cynthia L. Sears.

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C.L.S. has research funding from Bristol Myers Squibb and Janssen. The other authors declare no competing interests.

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Nature Cancer thanks Giorgio Trinchieri and Laurence Zitvogel for their contribution to the peer review of this work.

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Queen, J., Shaikh, F. & Sears, C.L. Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation. Nat Cancer 4, 1083–1094 (2023). https://doi.org/10.1038/s43018-023-00602-2

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