Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) presents a challenge for otolaryngologists due to its complex management and high recurrence rates. Glucocorticoids (GCs) are widely employed for their potent anti-inflammatory effects across various inflammatory conditions and play a pivotal role in treating CRS. However, some patients exhibit insensitivity to GC therapy, resulting in GC resistance (GCR). Oxidative stress is a key factor contributing to GCR development, whereas the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway functions as a vital cellular defense mechanism against oxidative stress-induced damage. Investigating the Nrf2 signaling pathway holds promise for advancing our understanding of GC sensitivity and refining its therapeutic application in CRS. This article reviews the relationship between GC sensitivity and the Nrf2 signaling pathway, as well as potential Nrf2-related drugs. Studies show that Nrf2 activators-when used alone or in combination with GCs-more effectively inhibit the release of inflammatory factors and mitigate oxidative stress damage than GC monotherapy, marking them as a promising target for CRS treatment.