Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: implications for future therapeutic approaches.
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.
Schleicher
Stephen M
SM
Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN, USA.
Moretti
Luigi
L
Varki
Vinod
V
Lu
Bo
B
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological
D000970:Antineoplastic Agents