Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms

Endoplasmic reticulum (ER) stress plays a pivotal role in tumor progression. As research in tumor biology advances, the relationship between ER stress and tumor initiation, development, and immune regulation has increasingly attracted attention. ER stress activates the unfolded protein response (UPR), thereby affecting key processes in tumor cells, including metabolism, proliferation, invasion, metastasis, and drug resistance. Moreover, it modulates tumor immune responses by regulating the functions of immune cells within the tumor microenvironment. This review consolidates the concept of ER stress as a central signaling hub that dictates cell fate and extensively remodels the tumor ecosystem. From a clinical perspective, this understanding provides a strong rationale for therapeutically targeting the UPR, suggesting that combining ER stress modulators with immunotherapy represents a promising strategy to overcome therapeutic resistance and improve patient outcomes.