Abstract
Pancreatic tumors are a serious health problem with a 7% mortality rate worldwide. Inflammatory processes and oxidative stress play important roles in the development of pancreatic diseases/cancer. To maintain homeostasis, a balance between free radicals and the antioxidant system is essential. Nuclear Factor Erythroid 2-Related Factor 2/NFE2L2 (Nrf2) and its negative regulator Kelch-Like ECH-Associated Protein 1 (Keap1) provide substantial protection against damage induced by oxidative stress, and a growing body of evidence points to the canonical and noncanonical Nrf2 signaling pathway as a pharmacological target in the treatment of pancreatic diseases. In this review, we present updated evidence on the activation of the Nrf2 signaling pathway and its importance in pancreatic cancer. Our review covers potential modulators of canonical and noncanonical pathway modulation mechanisms that may have a positive effect on the therapeutic response. Finally, we describe some interesting recent discoveries of novel treatments related to the antioxidant system for pancreatic cancer, including natural or synthetic compounds with therapeutic properties.
Highlights
The main environmental risk factors for pancreatic cancer, responsible for the development of approximately 30% of cancers, are: tobacco use, alcohol consumption, chronic pancreatitis, age (80% of cases occur between the ages of 60 and 80), obesity, and diabetes mellitus
Kim et al showed that the activation of Nuclear Factor Erythroid 2-Related Factor 2/NFE2L2 (Nrf2), caused by oxidative stress, protected pancreatic beta cells from damage and apoptosis, preventing pancreatic carcinogenesis induced by oxidants and carcinogens [69]
In two studies in which RSV was used in combination with other phytochemicals, a similar effect was confirmed. These results suggested that RSV promotes the apoptosis of pancreatic cancer cells via activation of the Nrf2 pathway and downregulates the NF-κB activity [70,71]
Summary
Pancreatic cancer is one of the most malignant neoplasms in the world, with current statistics indicating that it ranks third after colon and lung cancer with a mortality rate of about 6% in Western Europe and the USA and about 7% worldwide. It is worth indicating that pancreatic cancer is prognosticated to take over the second position by 2030 [1]. The literature’s data indicate that approximately 95% of pancreatic malignant neoplasms are in the exocrine glands and Antioxidants 2022, 11, 98. Antioxidants 2022, 11, 98 originate mainly from ductal cells. In 5% of pancreatic cancers, the cancer cells originate in the endocrine part of the pancreas and are called pancreatic neuroendocrine tumors (NETs) [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
