Adaptation to ER stress as a driver of malignancy and resistance to therapy in human melanoma.

Primary events in the development of melanoma are gradually being pieced together but a more complete picture of evolution of the disease requires additional understanding of secondary events consequent on initiation of the malignancy. Arguably, the most important driver of secondary events is signals resulting from induction of endoplasmic reticulum (ER) stress for example due to hypoglycaemia and anoxia. This may result in a variety of responses such as apoptosis, autophagy and senescence depending on the initiating event and cell type but most importantly it may result in progression of melanoma due to adaptation and selection of melanoma cells to ER stress. The following reviews what is known about the adaptive responses and how this information may provide new initiatives in treatment of the disease.