Methylglyoxal-induced cardonyl stress in melanoma progression and response to therapy

Cancer cells generally rely on aerobic glycolysis as a major source of energy and building blocks. Increased glycolysis in cancer cells leads to spontaneous production of Methylglyoxal (MG). This dicarbonyl compound is highly reactive and induces the formation of advanced glycation end-products implicated in several pathologies, including cancer. All mammalian cells have an enzymatic defense against MG, composed by glyoxalases GLO1 and GLO2, that converts MG to D-lactate. Aldo-keto reductase enzymes can also detoxify MG to acetol and lactaldehyde.
Melanoma, the most deadly form of skin cancer, is associated with BRAF or NRAS mutations. These mutations are characterized by a glycolytic switch thus leading to potential accumulation of MG stress.