Decoding the Role of Lipid Metabolism and Membrane Dynamics in Melanoma

Cutaneous melanoma is a highly aggressive type of cancer with a poor prognosis at advanced stages. Accumulating evidence demonstrates that metabolic reprogramming is essential for melanoma, allowing it to adapt to both cellular changes, due to its genetic instability, and to micro-environmental stimuli. This review provides an overview of how melanoma cells remodel membrane lipids during melanoma progression with a focus on how environmental stresses (e.g., UV radiation) affect tumor aggressiveness and therapy resistance by reshaping membrane structure, fluidity, and composition. Dietary lipids, especially omega-3 polyunsaturated fatty acids (PUFAs), further modulate membrane properties and can sensitize melanoma cells to oxidative stress and ferroptosis, revealing potential therapeutic vulnerabilities. Finally, we discuss emerging evidence that lipid signatures, including circulating lipid profiles and melanoma-derived exosomes, have prognostic and predictive value. Together, these insights emphasize the importance of lipid metabolism and membrane architecture as key factors in melanoma biology and as promising targets for personalized interventions.