Melanoma Metabolism

The rewiring of metabolic pathways is one of the hallmarks of cancer and essential for tumorigenesis. It stems from the need of cancer cells to adapt their biosynthetic and bioenergetic demands in order to allow unrestricted proliferation and growth. Melanoma and other cancer cells exhibit a remarkable flexibility within a complex network of metabolic pathways, allowing them to use their often limited resources and direct them to the processes best placed to maximize their growth and survival. For example, during melanomagenesis, cells will often switch their energy production from mitochondrial metabolism to glycolysis, because the products of glycolysis can easily be shifted to essential pathways for macromolecule biosynthesis. Many of these metabolic alterations are initiated in response to signaling cues from genetic alterations that initiated melanomagenesis in the first place, which suggests that the events required to transform cells to malignancy must allow cells to meet their biosynthetic and bioenergetic needs. During progression, melanomas appear to display metabolic heterogeneity as vital nutrient sources become scarce and the tumor seeks to overcome these restrictions. As further insights into the metabolic rewiring that occurs during melanoma development and progression are gained, opportunities to target these vulnerabilities for therapeutic benefit may be exploited. This book chapter provides a brief overview of important metabolic pathways and how these become reprogrammed by known oncogenes that are frequently altered in human melanomas. How these metabolic vulnerabilities are being targeted for clinical use will also be highlighted.