Why is autophagy important for melanoma? Molecular mechanisms and therapeutic implications

As the principle lysosomal mediated mechanism for the degradation of aged or damaged organelles and proteins, autophagy (self-eating) is generally considered a pro-survival process activated by cells to sustain life in presence of adverse environmental conditions such as nutrient shortage and/or in presence of cytotoxic compounds [1]. Upon activation, cytoplasmic material is sequestered into double-membrane vesicles (autophagosomes) then targeted for degradation by fusion with lysosomes (autolysosomes); metabolic activity and cell survival are consequently sustained by recycling the degradation products. Basal autophagy occurs in almost all cell types, though at different degree, as a finely regulated “quality control” process to prevent cell damage, for the demolition of cellular structures during cell/tissue remodelling, and to ensure the maintenance of cellular homeostasis through recycling cellular components/molecules [2] and [3].Autophagy is stimulated in response to both physiological and pathological conditions such as starvation, hypoxia and low energy, pathogen infection and protein aggregates.Although it's clear that autophagy is also involved in cancer, its role, however, is complex since it can both suppress and promote tumorigenesis [4]. Consequently, it is generally accepted that while autophagy is used by advanced stage cancers to maintain tumour survival, loss of autophagy in earlier stages is associated with tumour development.Accordingly, it is now apparent that aberrant control of autophagy is among key hallmarks of cancer, with several studies now demonstrating this process is deregulated also in melanoma [5] and [6].