Cancer stem cell as therapeutic target for melanoma treatment.
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.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA.
Abdulhadi A
AA
Alamodi
Alfaisal University, College of Medicine, Riyadh, Kingdom of Saudi Arabia.
Abdulaziz M
AM
Eshaq
Clinic of Dermatology, University Hospital of Aachen, Aachen, Germany.
Sofie-Yasmin
SY
Hassan
Department of Pathology, University of Mississippi Medical Center, Jackson, USA.
Youssef
Y
Al Hmada
Department of Pathology, University of Mississippi Medical Center, Jackson, USA.
Siraj M
SM
El Jamal
Alfaisal University, College of Medicine, Riyadh, Kingdom of Saudi Arabia.
Ahmed M
AM
Fothan
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA, University of Mississippi Medical Center, Jackson, USA.
Omair M
OM
Arain
Clinic of Dermatology, University Hospital of Aachen, Aachen, Germany.
Sarah-Lilly
SL
Hassan
Institut National de la Santé et de la Recherche Médicale, Strasbourg, France.|Clinic of Operative Dentristy and Endodonties, Dental Faculty, University of Strasbourg, Strasbourg, France.
Youssef
Y
Haikel
Clinic of Dermatology, University Hospital of Aachen, Aachen, Germany.
Mosaad
M
Megahed
Department of Pathology, University of Mississippi Medical Center, Jackson, USA.|Clinic of Operative Dentristy and Endodonties, Dental Faculty, University of Strasbourg, Strasbourg, France.|Cancer Institute, University of Mississippi Medical Center, Jackson, USA. dr.hassan@gmx.de.
Mohamed
M
Hassan
D006801:Humans; D008545:Melanoma / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma