Roles of microbiota in pancreatic cancer development and treatment

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. This is due to the fact that most cases are only diagnosed at an advanced and palliative disease stage, and there is a high incidence of therapy resistance. Despite ongoing efforts, to date, the mechanisms underlying PDAC oncogenesis and its poor responses to treatment are still largely unclear. As the study of the microbiome in cancer progresses, growing evidence suggests that bacteria or fungi might be key players both in PDAC oncogenesis as well as in its resistance to chemo- and immunotherapy, for instance through modulation of the tumor microenvironment and reshaping of the host immune response. Here, we review how the microbiota exerts these effects directly or indirectly via microbial-derived metabolites. Finally, we further discuss the potential of modulating the microbiota composition as a therapy in PDAC.

KEYWORDS:

• Pancreatic cancer
• pancreatic ductal adenocarcinoma
• PDAC
• oncogenesis
• microbiota
• bacteria
• fungi
• therapy resistance
• microbiota-derived metabolites

Acknowledgments

We thank Madeleine Hamley for proofreading the review. This work is supported by a grant from the German Cancer Aid to J.T. and N.G. (70114815). During the preparation of this work the authors used chat.openai.com in order to proofread few sentences. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Disclosure statement

NG reports financial support from F. Hoffmann-La Roche. This is outside the submitted work. All other authors declare no conflict of interest.

Author contributions

MSC wrote the manuscript and prepared the figure. JT and NG co-supervised the work, reviewed and edited the manuscript and the figure.

Additional information

Funding

The work was supported by the Deutsche Krebshilfe [70114815].