Metabolic Biomarkers of Therapeutic Response in YUMM1.7 Melanoma Targeting BRAF and MEK Inhibition

Motivation: Monitor the metabolic effects of a combined dabrafenib and trametinib therapy in YUMM1.7 melanoma models using 1H/31P MRS. Goal(s): Test the metabolic effects of the combined BRAF and MEK inhibition in YUMM1.7 melanoma models. Approach: We use in vivo, 1H/31P MRS, tests to measure lactate, alanine, bioenergetics (β-NTP/Pi), and NAD(H). We aim to test whether they are early, sensitive biomarkers for the combined therapy response in the YUMM1.7 melanoma model. Results: Rapid changes in lactate, alanine, bioenergetics, and NADH in response to combined dabrafenib and trametinib therapy are closely linked to subsequent tumor response. Impact: This study shows that combining dabrafenib and trametinib may block the overactive BRAF and MEK proteins. Variations in critical metabolites (lactate and alanine), bioenergetics, NADH, and pH may explain differential therapeutic responses in YUMM1.7 melanoma models.