Cancer stem cell as therapeutic target for melanoma treatment
Abdulhadi A. Alamodi1, Abdulaziz M. Eshaq2, Sofie-Yasmin Hassan3, Youssef Al Hmada4, Siraj M. El Jamal4, Ahmed M. Fothan2, Omair M. Arain1, Sarah-Lilly Hassan3, Youssef Haikel5,6, Mosaad Megahed3 and Mohamed Hassan4,5,7
1Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA, 2Alfaisal University, College of Medicine, Riyadh, Kingdom of Saudi Arabia, 3Clinic of Dermatology, University Hospital of Aachen, Aachen, Germany, 4Department of Pathology, University of Mississippi Medical Center, Jackson, USA, 5Institut National de la Santé et de la Recherche Médicale, 6Clinic of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, Strasbourg, France and 7Cancer Institute, University of Mississippi Medical Center, Jackson, USA
Offprint requests to: Dr. Mohamed Hassan, Cancer Institute, University of Mississippi, Medical Center, Jackson, MS, USA. e-mail: dr.hassan@gmx.de
Summary. Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment. Histol Histopathol 31, 1291-1301 (2016)
Key words: Melanoma, Cancer stem-like cells, Melanoma stem cells, Signaling pathways, Therapy
DOI: 10.14670/HH-11-791