Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment

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.