Regulation of Ubiquitin-Proteasome System and Its Relative Pathways in Pancreatic Adenocarcinoma Publisher



Amiri BS¹ ; Naserranjbar M² ; Mirhaji A³ ; Hejrati A² ; Hejrati L² ; Aliabadi F⁴ Show Affiliations
Source: BioImpacts Published:2025

Abstract

Introduction: Pancreatic cancer, which results from the uncontrolled growth of pancreatic cells, is the fourth most frequent cause of cancer-related mortality in the United States. About 90% of instances of pancreatic cancer are pancreatic adenocarcinomas, and occasionally pancreatic cancer is used exclusively to describe this subtype. Nab-paclitaxel, gemcitabine, and FOLFIRINOX are examples of modern chemotherapeutic drugs that have the ability to quickly confer resistance in pancreatic tumor cells. Therefore, in order to treat this dreadful condition, it is essential to develop more effective medicines. Inhibition of the ubiquitin-proteasome system (UPS) causes pancreatic cancer cells to die apoptotically. In eukaryotes, UPS is an essential mechanism for protein breakdown. Pancreatic cancer cells are more susceptible to endoplasmic reticulum stress (endoplasmic reticulum [ER] stress) and apoptosis when treated with bortezomib, a proteasome inhibitor that is the first in this group of drugs approved for the treatment of cancer, especially multiple myeloma. Methods: Searching through PubMed and Google Scholar and gathering data. Results: UPS is still a popular target for pancreatic cancer treatment among researchers. However, despite the favorable results of UPS-based therapies in vitro and in vivo, the clinical results are not as promising as expected. Conclusion: A deep understanding of it, is essential to achieving the maximum results. In this review, we aim to look into the UPS along with searching for the novelist therapies for pancreatic adenocarcinoma based on manipulating it. © 2025 The Author(s).