Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: Implications for future therapeutic approaches

• Published in: Drug resistance updates Vol. 13; no. 3; pp. 79 - 86
• Main Authors: Schleicher, Stephen M, Moretti, Luigi, Varki, Vinod, Lu, Bo
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-06-2010
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Apoptosis - physiology; Autophagy; Autophagy - drug effects; Autophagy - physiology; Bortezomib; Cancer; Cell Survival - drug effects; Combined Modality Therapy; Drug Resistance, Neoplasm; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - physiology; Endoplasmic reticulum stress; Hematology, Oncology and Palliative Medicine; HIV protease inhibitor; Humans; Infectious Disease; Mice; Neoplasms - drug therapy; Neoplasms - physiopathology; Neoplasms - radiotherapy; Radiation; Selenium; Signal Transduction - drug effects; Stress, Physiological; Bortezomib; Radiation; HIV protease inhibitor; Selenium; Autophagy; Endoplasmic reticulum stress; Cancer
• ISSN: 1368-7646; 1532-2084
• DOI: 10.1016/j.drup.2010.04.002

Abstract Given the inherent resistance to apoptosis that characterizes cancer, the targeting of alternative pathways is an attractive strategy to improve anti-tumor therapy. Endoplasmic reticulum (ER) stress, which is basally activated in many cancers, and the subsequent activation of autophagy represent novel cancer treatment targets. While these associated pathways are often protective and promote cell survival, when excessive, ER stress results in autophagic cell death. Therefore, depending on the circumstances, either inhibition or activation of ER stress and autophagy can improve cancer therapy. This review provides an update on how ER stress relates to autophagy, and how these associated pathways can serve dual functions to promote survival or cell death in cancer. Furthermore, it lays out a spectrum of potential pharmacological agents and combinatorial approaches that target these pathways to enhance tumor cell kill.