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The Markers and Tissue Resources for Melanoma meeting convened by the Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, Specialized Programs of Research Excellence at the Organ Systems Branch of the National Cancer Institute (NCI), and the Melanoma Research Foundation was held in Gaithersburg, MD on October 2005. The meeting reviewed the current status of biomarkers for early- and advanced-stage melanoma and addressed some of the challenges scientists and clinicians face as they unravel the biology of melanoma and try to apply these findings to patient care. Specifically, the participants focused on molecular changes associated with melanoma progression, potential diagnostic and prognostic markers emerging from molecular profiling studies, and new treatment targets for current and future clinical trials. They also highlighted the ongoing challenges about translational research in melanoma, including availability of tissue resources, and summarized the status of nevus and melanoma tissue microarrays, recently developed as a collaborative project between the melanoma research community and the NCI. The meeting report is intended to provide a perspective on emerging scientific approaches in translational research that can enhance the progress in discovery and validation of markers for melanoma. (Cancer Res 2006; 66(22): 10652-7)

Mitochondria are important gatekeepers of cell survival in melanoma cells and their role as oxygen sensors, ATP producers, or inducers of reactive oxygen species are established. However, the role(s) of metabolic processes other than glycolysis are not well characterized in melanoma development and progression. Here we show that melanoma cells exhibit higher levels of oxidative phosphorylation (Oxphos) compared to human epidermal melanocytes. Furthermore, we present several independent lines of evidence (bioenergetics analysis using Seahorse XF24, stable isotope labeling of melanoma cells in culture, immunoblot analysis of isolated mitochondria, electron microscopy, and rho zero cells) that elesclomol, an inducer of oxidative stress, suppresses Oxphos in melanoma cells without a significant effect on glycolysis in vitro. Melanoma cells with intrinsically high levels of glycolysis are less sensitive to elesclomol. In addition, following chronic continuous drug exposure, resistant cells manifest a high glycolytic phenotype. Finally hypoxia inducible factor 1 alpha, a master metabolic switch of cell metabolism towards glycolysis, is upregulated following elesclomol treatment in a number of melanoma cell lines examined. Our results suggest that Oxphos is an important therapeutic target and that elesclomol specifically impinges on this process. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B144.