NF-κB Mediated Disruption of Pancreatic Signaling Pathways and its Implications for the Risk of Pancreatic Adenocarcinoma: a systematic review

Abstract

ObjectiveThe objective of this study is to determine how NF-κB-mediated inflammation disrupts pancreatic signaling pathways and the resultant increase in the risk of Pancreatic Adenocarcinoma.BackgroundPancreatic adenocarcinoma’s severity and poor prognosis underscore the critical role of NF-κB-mediated inflammation in disease progression. NF-κB activation disrupts key pancreatic signaling pathways by promoting cell proliferation, inhibiting differentiation, and facilitating oncogenic transformation. Understanding these mechanisms is essential for developing targeted therapies that mitigate NF-κB-induced damage, improve early detection through biomarkers, and enhance treatment outcomes for pancreatic cancer patients.MethodsDatabases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate how NF-κB-mediated inflammation disrupts pancreatic signaling pathways and the resultant increase in the risk of Pancreatic Adenocarcinoma. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate the research question. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).ResultsNF-κB-mediated inflammation significantly disrupts several critical pancreatic signaling pathways, leading to oncogenic transformations and increased risk of pancreatic adenocarcinoma. Specifically, NF-κB activation alters Notch signaling, causing abnormal cell differentiation; disrupts Wnt and Shh pathways, enhancing cellular proliferation; and perturbs FGF and TGF-β pathways, leading to impaired cellular homeostasis. Additionally, NF-κB interferes with BMP signaling, contributing to dysregulated cell growth; modulates the PI3K/Akt/mTOR pathway, promoting cell survival and tumor growth; affects JAK/STAT signaling, resulting in enhanced inflammatory responses and tumor progression; and disrupts Hippo pathway components, which normally regulate organ size and inhibit tumorigenesis.ConclusionNF-κB-mediated inflammation disrupts critical pancreas signaling pathways—Notch, Wnt, Hippo, JAK/STAT, and others—promoting cell survival, proliferation, and oncogenic transformation. This dysregulation, seen in chronic inflammation, elevates pancreatic adenocarcinoma risk by fostering a tumorigenic microenvironment. These interactions highlight NF-κB as a central player in pancreatic cancer pathogenesis. Targeting NF-κB and associated pathways emerges as crucial for therapeutic strategies aimed at mitigating inflammatory damage and improving outcomes in pancreatic adenocarcinoma treatment.