Pancreatic Cancer, Inflammation, and Microbiome

Abstract

Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist and available treatment modalities do not effectively treat the disease. Inflammatory conditions such as pancreatitis represent a well-known risk for pancreatic cancer development. Yet only in the past two decades has pancreatic cancer been recognized as an inflammation-driven cancer, and the precise mechanisms underlying the pathogenic role of inflammation are beginning to be explored in detail. A substantial amount of preclinical and clinical evidence suggests that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. The recent explosion of investigations into the human microbiome have highlighted how perturbations of commensal bacterial populations can promote inflammation and promote disease processes, including carcinogenesis. The elucidation of the interplay between inflammation and microbiome in the context of pancreatic carcinogenesis will provide novel targets for intervention in order to both prevent and treat pancreatic cancer more efficiently. Further studies towards this direction are urgently needed.

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

“…In this study, we considered knowledge associating tumor inflammation both with pancreatic cancer (42) and with the modulation of the nerve compartment (43,44) to reach our hypothesis that stromal-driven inflammatory genes/pathways could, additionally to their effects on tumor cells, impact the nerve compartment and in particular PANR. Thus, we revisited previous transcriptomic analysis (Gene Expression Omnibus (GEO): GSE50570 for human PDA, (12), and GSE61412 for mouse PDA, (27) and highlighted numerous genes that code for molecules involved in gp130 signaling and were overexpressed in the PDA stromal compartment compared to PDA tumor cells.…”

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle

“…Recently, periodontal disease and limited oral hygiene have been recognized as risk factors for pancreatic cancer, as they facilitate the translocation of bacteria (Zambirinis et al, 2014). As reported by Mitsuhashi et al (2015), bacteria can reach the pancreas through circulation, and it has been suggested that this occurs through the biliary tract (transductal transmission) (Zambirinis et al, 2014) to act synergistically with other risk factors, such as obesity and smoking, among others, during carcinogenesis.…”

“…Although not yet well described, the most readily accepted mechanism is the activation of the immune system, and the perpetuation of inflammation associated with the tumour, rather than direct mutagenicity (Zambirinis et al, 2014). As with the liver, the pancreas does not present a known microbiome, but it is presumed that carcinogenesis in this organ is supported by distant dysbiotic microbiota (Schwabe & Jobin, 2013).…”

“…Pancreatic cancer is an aggressive malignancy, with a low rate of survival and therapeutic success (Mitsuhashi et al, 2015;Pevsner-Fischer et al, 2016). Therefore, it is important to further understand its pathogenesis and to search for new diagnostic and therapeutic alternatives (Mitsuhashi et al, 2015;Zambirinis et al, 2014).…”

Hereditary Pancreatic Cancer

“…The human microbiome is altered by several environmental factors along with host hygiene such as alcohol use, periodontitis, and the use of antibiotics. The microbiome may play a greater role in inflammation and the eventual development of several malignancies, including pancreatic cancer [62]. A study examining the microbiome by oral wash samples from 361 individuals who developed pancreatic cancer and comparing it to 371 matched controls showed the presence of two species of bacteria, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans associated with an increased risk of pancreatic cancer [63].…”