Detection of Metabolic Biomarkers of Response to BRAF and MEK Inhibitor Therapy of Melanoma
Pradeep Kumar Gupta1, Stepan Orlovskiy1, David S. Nelson1, Stephen Pickup1, Alexander A. Shestov1, Fernando Arias-Mendoza1, Mary E. Putt2, Dennis B. Leeper3, Jerry D. Glickson1, and Kavindra Nath1
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States
In vivo 1H and 31P MRS were used to monitor the effects of BRAF and MEK inhibitors therapy in two metabolically different melanoma xenograft models. Our approach is to combine BRAF inhibitor with MEK inhibitor in melanoma xenograft models. Combination of BRAF and MEK inhibitors has been shown to be more effective than the use of either drug alone. Differences in relative levels of glycolysis between two melanoma xenograft models may produce differential therapeutic responses to BRAF and MEK inhibitors . In melanoma, metabolic changes in response to targeted kinase inhibitor therapy occur rapidly and are related to subsequent tumor response.
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