The microbiome, cancer, and cancer therapy

Abstract

With the advent of next-generation sequencing, we have an unprecedented ability to study tumor and host genomes as well as those of the vast array of microorganisms that exist within living organisms. Evidence now suggests that these microbes may confer susceptibility to certain cancers and may also influence response to therapeutics. A prime example of this is seen with immunotherapy, for which gut microbes have been implicated in influencing therapeutic responses in preclinical models and patient cohorts. However, these microbes may influence responses to other forms of therapy as well and may also affect treatment-associated toxicity. Based on these influences, there is growing interest in targeting these microbes in the treatment of cancer and other diseases. Yet complexities exist, and a deeper understanding of host–microbiome interactions is critical to realization of the full potential of such approaches. These concepts and the means through which such findings may be translated into the clinic will be discussed herein.

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Fig. 1: The influence of gut microbiota on cancer development.
Fig. 2: The influence of the gut microbiota on different cancer therapies.
Fig. 3: Existing evidence for the role of the gut microbiota in cancer development and treatment response.
Fig. 4: Strategies to target the gut microbiota.

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Correspondence to Jennifer A. Wargo.

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J.A.W. and V.G. are inventors on a US patent application (PCT/US17/53,717), submitted by The University of Texas MD Anderson Cancer Center, that covers methods to enhance checkpoint blockade therapy by the microbiome. J.A.W. reports compensation for speaker’s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune and Bristol-Myers Squibb. J.A.W. serves as a consultant / advisory board member for Roche/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Biothera Pharmaceuticals and Microbiome DX. J.A.W. also receives research support from GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, and Novartis. A.C-H. and M.A.W.K. report no relevant conflicts of interest or financial disclosures. B.A.H. is supported by National Institutes of Health T32 CA 009599 and the MD Anderson Cancer Center support grant P30 CA016672.

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Helmink, B.A., Khan, M.A.W., Hermann, A. et al. The microbiome, cancer, and cancer therapy. Nat Med 25, 377–388 (2019). https://doi.org/10.1038/s41591-019-0377-7

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