Abstract
Organoids represent an advanced tool in cell biology and have redefined biomedical research. Organoids are ideal for studies of biological processes, pharmacological studies, and therapeutic research to imitate pathological processes and preserve genetic integrity. The endoplasmic reticulum (ER) is the central organelle responsible for protein folding, post-translational adaptations, and membrane and luminal protein transportation. ER stress is a disorder influenced by a range of physiological and pathological causes, such as nutrient deficiency, impaired glycosylation, calcium depletion, oxidative stress, DNA damage, and energy disruption. Disturbance of the ER environment triggers aggregation of unfolded/misfolded proteins, accelerating ER stress. The unfolded protein response (UPR) is a transduction mechanism that activates cells in response to ER stress to restore ER homeostasis, altering cancer development and progression. However, the mechanisms through which sustained and unresolved UPR signaling triggers a switch from pro-survival to pro-death pathways remain unclear. Immutable and environmental stimuli that modify protein homeostasis are often incorporated into tumor cells, thereby generating ER stress. Herein, we discuss challenges and advances in fundamental and clinical cancer studies on ER stress. Additionally, current trends in organoid technology are summarized to fill the gap in our knowledge of the relationship between cancer and ER stress, with the UPR representing a future tool for investigating drug response screening and potentially revolutionizing the workflow of new cancer drug development.