title: Autophagy: In the cROSshairs of cancer.
abstract: Two prominent features of tumors that contribute to oncogenic survival signaling are redox disruption, or oxidative stress phenotype, and high autophagy signaling, making both phenomena ideal therapeutic targets. However, the relationship between redox disruption and autophagy signaling is not well characterized and the clinical impact of reactive oxygen species (ROS)-generating chemotherapeutics on autophagy merits immediate attention as autophagy largely contributes to chemotherapeutic resistance. In this commentary we focus on melanoma, using it as an example to provide clarity to current literature regarding the roles of autophagy and redox signaling which can be applicable to initiation and maintenance of most tumor types. Further, we address the crosstalk between ROS and autophagy signaling during pharmacological intervention and cell fate decisions. We attempt to elucidate the role of autophagy in regulating cell fate following treatment with ROS-generating agents in preclinical and clinical settings and discuss the emerging role of autophagy in cell fate decisions and as a cell death mechanism. We also address technical aspects of redox and autophagy evaluation in experimental design and data interpretation. Lastly, we present a provocative view of the clinical relevance, emerging challenges in dual targeting of redox and autophagy pathways for therapy, and the future directions to be addressed in order to advance both basic and translational aspects of this field.
authors: Department of Urology, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors: Heather Graham
authors: HG
authors: Hambright
authors: Department of Urology, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Pharmacology, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, South Texas Research Facility Campus, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: ghoshr@uthscsa.edu.
authors: Rita
authors: R
authors: Ghosh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D058990:Molecular Targeted Therapy; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D006834:Hydrazines; D017382:Reactive Oxygen Species; C512195:elesclomol
keywords: Autophagy; Cancer; Cell fate; Reactive oxygen species; Therapy