The Role and Mechanism of Unfolded Protein Response Pathway in Tumor Drug Resistance

Abstract

In the process of tumor proliferation and metastasis, tumor cells encounter hypoxia, low glucose, acidosis, and other stressful environments. These conditions prompt tumor cells to generate endoplasmic reticulum stress (ERS). As a signal mechanism that mitigates ERS in eukaryotic cells, the unfolded protein response (UPR) pathway can activate cells and tissues, regulating pathological activities in various cells, and maintaining ER homeostasis. It forms the most crucial adaptive and defensive mechanism for cells. However, under the continuous influence of chemotherapy drugs, the quantity of unfolded proteins and erroneous proteins produced by tumor cells significantly increases, surpassing the normal regulatory range of UPR. Consequently, ERS fails to function properly, fostering tumor cell proliferation and the development of drug resistance. This review delves into the study of three UPR pathways (PERK, IRE1, and ATF6), elucidating the mechanisms of drug resistance and research progress in the signal transduction pathway of UPR related to cancers. It provides a profound understanding of the role and relationship between UPR and anti-tumor drugs, offering a new direction for effective clinical treatment.