The role and therapeutic implication of endoplasmic reticulum stress in inflammatory cancer transformation

Endoplasmic reticulum (ER) stress occurs when proteins are affected by various factors, fail to fold properly into higher structures and accumulate in the lumen of the ER, which activates the unfolded protein response (UPR) to restore normal cellular function or induce apoptosis as a self-protective mechanism. However, a growing number of studies have shown that the three branches of ER stress and the UPR can mediate inflammation and cancer development by interacting with inflammatory transformation-related signaling pathways. Targeting the UPR, especially the use of small molecules that target the active sites of the enzymes IRE1α and PERK and BIP/GRP78 inhibitors are potential strategies for treating tumors and have shown promising results in some tumor models. Therefore, in this review, we summarize the progress of ER stress/UPR research and the signaling pathways associated with inflammatory cancer transformation, provide an in-depth description of the mechanisms of these pathways, and outline strategies in the field of UPR biology in tumor therapy to provide new ideas for the mechanisms of inflammatory cancer transformation and tumor-related treatment.