Unfolded protein response complexity in gynecological tumor dynamics: therapeutic challenges and future perspectives

Cancer cells frequently undergo stresses like hypoxia, glucose deprivation, and calcium depletion, leading to protein misfolding and accumulation of unfolded proteins in the ER, which trigger ER stress. The unfolded protein response (UPR) is activated by endoplasmic reticulum (ER) stress to restore protein homeostasis by regulating protein synthesis and degradation. This review explores the multifaceted role of UPR in tumor growth, chemoresistance, and immune evasion in gynecological cancers, particularly ovarian, endometrial, and cervical cancers. UPR-associated genes have been reported to have a potential role as disease biomarkers and therapeutic targets, thus improving early detection and personalized treatment. This review aims to give insights into the role of UPR pathway in gynecological cancers and offers new perspectives for future research and clinical applications.