Endoplasmic Reticulum Stress and Autophagy in Cancer

Endoplasmic Reticulum stress (ER stress) is a condition whereby unfolded and misfolded proteins accumulate in the ER lumen as a result of perturbation of the ER homeostasis. Nutrient deprivation, hypoxia, and calcium depletion are some conditions which can compromise the homeostasis of this compartment. To overcome the imbalanced ER protein-folding capacity, cells have evolved an evolutionary conserved signal transduction pathway called unfolded protein response (UPR) which primarily aims to reestablish ER homeostasis. Meanwhile, autophagy is a process responsible for the turnover of unnecessary or dysfunctional organelles and proteins. It facilitates normal cell growth and development and it is also a survival pathway, required during starvation or growth factor deprivation. Massive vacuolation as a result of uncontrolled autophagy leads to cell death. It is now widely acknowledged that various proteins and pathways related to ER stress and autophagy are deregulated during cancer development. This chapter highlights the signaling pathways of ER stress and autophagy, the relevant therapeutic targets in cancer, and summarizes the current state of development of novel therapeutics in various phases of clinical trials. In addition, crosstalks in apoptosis, autophagy, and ER stress signaling pathways and future treatment strategies are reviewed.