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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Nov 20, 2015; 5(4): 206-217
Published online Nov 20, 2015. doi: 10.5493/wjem.v5.i4.206
Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment
Mohamed Hassan, Denis Selimovic, Matthias Hannig, Youssef Haikel, Robert T Brodell, Mossaad Megahed
Mohamed Hassan, Denis Selimovic, Matthias Hannig, Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, University Hospital, Saarland University, D-66421 Homburg/Saar, Germany
Mohamed Hassan, Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, United States
Mohamed Hassan, Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, United States
Mohamed Hassan, Youssef Haikel, Institut National de la Santé et de la Recherché Medical, U1121, University of Strasbourg, 67000 Strasbourg, France
Youssef Haikel, Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
Robert T Brodell, Department of Dermatology, University of Mississippi Medical Center, Jackson, MS 39216, United States
Mossaad Megahed, Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany
Author contributions: Hassan M designed and wrote the paper; Selimovic D, Hannig M, Haikel Y, Brodell RT and Megahed M wrote the paper.
Conflict-of-interest statement: Authors have no conflict-of-interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Mohamed Hassan, Cancer Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States. dr.hassan@gmx.de
Telephone: +1-601-8158945 Fax: +1-601-9842981
Received: March 27, 2015
Peer-review started: March 28, 2015
First decision: May 13, 2015
Revised: July 29, 2015
Accepted: September 7, 2015
Article in press: September 8, 2015
Published online: November 20, 2015
Processing time: 241 Days and 7.3 Hours
Abstract

Melanoma is the most aggressive form of skin cancer. Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation, there is increasing evidence that endoplasmic reticulum (ER) stress-associated pathways play a role in the potentiation, initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment.

Keywords: Melanoma; Endoplasmic reticulum; Apoptosis; Autophagy; Signaling pathways; Chemotherapy

Core tip: This editorial describes the clinical validity of the endoplasmic reticulum (ER) as therapeutic target for melanoma treatment. In addition, we highlight in this review the mechanistic role of ER stress in the modulation of both apoptosis and autophagy- associated pathways. Drugs that perturb ER function may represent an alternative approach for melanoma treatment. This paper reviews the pervious and current published studies on the reliability of ER-associated pathways as therapeutic targets for melanoma.