Role of the microbiome in occurrence, development and treatment of pancreatic cancer

Abstract

Pancreatic cancer is one of the most lethal malignancies. Recent studies indicated that development of pancreatic cancer may be intimately connected with the microbiome. In this review, we discuss the mechanisms through which microbiomes affect the development of pancreatic cancer, including inflammation and immunomodulation. Potential therapeutic and diagnostic applications of microbiomes are also discussed. For example, microbiomes may serve as diagnostic markers for pancreatic cancer, and may also play an important role in determining the efficacies of treatments such as chemo- and immunotherapies. Future studies will provide additional insights into the various roles of microbiomes in pancreatic cancer.

Keywords: Chemotherapy; Diagnosis; Microbiomes; Pancreatic cancer.

Fig. 1

Microbiomes play important roles in the development and treatment of pancreatic cancer. The blue arrow indicates that microbiome exposure activates inflammation to promote development of pancreatic cancer. The orange arrow shows that the microbiome leads to immune suppression. The green arrow shows that the microbiome influences the effects of cancer treatments. AHL-12, N-acetyl-dodecanoyl homoserine; T2R38, one of the family of bitter receptors; mTOR, mammalian target of rapamycin; LPS, lipopolysaccharide; TLR, Toll-like receptor; AP-1, Activator protein 1; STAT3, Signal transducers and activators of transcription 3; Th1/2, helper T cell 1/2; PD-1, programmed cell death-1; CDD, cytidine deaminase; 2′,2′-difluorodeoxycytidine, gemcitabine; 2′,2′-difluorodeoxyuridine, an inactive form of gemcitabine

Fig. 2

Microbiomes are involved in the occurrence pancreatic cancer. Microbiomes can lead to development of inflammation, inhibit interactions between macrophages and T cells, and favor Th2 polarization of the T cell response. All of these factors can contribute to the occurrence of pancreatic cancer. GFR, growth factor receptor; TGF-β, transforming growth factor-β; TbR, transforming growth factor-β receptor; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α; TNFR, tumor necrosis factor receptor