Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

SIMPLE SUMMARY: Oxidative stress occurs when the balance between oxidants and antioxidant factors is disrupted in biological systems. This is a key field of study likely involved in many diseases, including skin cancers. In this respect, the oxidative stress phenotype in melanoma cells is well established as well as the connections with autophagy, an evolutionarily conserved catabolic process in eukaryotes that has an essential role in maintaining melanoma cellular homeostasis in response to intracellular stress. Herein, we present the evidence for drugs and treatments that are able to modulate melanoma cell fate via oxidative stress and autophagy, since the development of successful therapies in skin cancer depends on a more complete understanding of the cross-talk between these events and their pharmacological targeting. ABSTRACT: Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.