Tehran University of Medical Sciences Basic & Clinical Cancer Research 2228-6527 9 2 2017 12 25 38 48 EN Marveh Rahmati Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran Saeid Amanpour Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran Amirhossein Razavirad Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran Mohammad Amin Moosavi Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran 2017 09 06 2017 11 13 Perturbation of endoplasmic reticulum (ER) homeostasis induces a stress condition described as “ER stress”, which in turn leads to a well-regulated program termed as unfolded protein response (UPR). The principal purpose of UPR is to reestablish the ER homeostasis. Some of the physiological and pathological situations that disrupt the homeostasis include hypoxia, glucose limitations, nutrient deprivation, low pH, genomic instability, and some cytotoxic compounds are frequently observed during the core formation and progression of tumors. These stressful microenvironments around the tumors affect the innate and adaptive immune responses. The ER stress is usually induced to activate the UPR and to handle the stress. Although the UPR mechanism is primarily a pro-survival process, preserved and/or prolonged stress may induce cell death. In tumors, ER stress may modify apoptotic and autophagic cell death and, thereby provokes drug resistance of cancerous cells to current therapies. In this mini-review, at first, we highlight the role of UPR and its mediators in cancerous cells fate and then discuss their potential opportunities in cancer therapy. https://bccr.tums.ac.ir/index.php/bccrj/article/view/252