Review

Role of Reactive Oxygen Species and Targeted Therapy in Metastatic Melanoma

 

Rosalin Mishra*,Hima Patel*,Long Yuan, Joan T. Garrett#

*These authors contributed equally

#Corresponding Author: Joan T. Garrett, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0514  

Phone: 513-558-6662; Fax: 513-558-4372; Email: joan.garrett@uc.edu

 

Abstract

Reactive oxygen species (ROS) play a significant role in various stages of melanoma development including melanocytes transformation, melanin production, melanoma cell metabolism, metastasis and immune response against melanoma progression. Several molecular and enzymatic signaling cascades control ROS levels and have differential regulation depending on the cell types. The equilibrium between ROS production and scavenging is crucial for maintaining cellular homeostasis and this balance is often altered in tumor cells. ROS is generated in cancer cells due to mitochondrial dysfunction, enhanced metabolic rates, increased cellular signaling, enhanced peroxisome activities and genetic alterations. In this review, we discuss the source and the mechanism of ROS generation. We also highlight the role of ROS in the process of melanomagenesis. This review provides an overview of ROS-dependent anti-cancer therapies including ROS scavenging antioxidants and ROS boosting therapies which have presented promising outcomes both in in vitro and in vivo melanoma models. We summarize how the understanding of ROS-targeted signaling plays a crucial role in melanoma prognosis and drug resistance. Hence, the knowledge of ROS in melanoma etiology and progression can be exploited in the clinical practice for development of better therapies for melanoma treatment.

 

Keywords: Melanoma, ROS, BRAF, antioxidant, targeted therapy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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