An imbalance of protein homeostasis caused by external or internal stress in the endoplasmic reticulum triggers the initiation of signalling pathways downstream of the IRE1, ATF6 and PERK sensors to a translational or transcriptional adaptive response known as UPR (Unfolded Protein Response). According to the intensity and duration of stress, the dual function of the UPR leads to either cell adaptation or cell death. UPR pathways in cancer cells are often altered and generally lead to an adaptation to an hostile environment. As the UPR becomes an emerging therapeutic target due to its increasing contribution to various diseases, we describe in this review various strategies that have been developed to discover new compounds enabling to manipulate the magnitude of ER stress in the context of cancer.
© 2015 médecine/sciences – Inserm.