Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma

Motivation: We use 1H/31P MRS to monitor the metabolic effects of dabrafenib therapy in four human melanoma models, an FDA-approved treatment for late-stage melanoma. Goal(s): Differences in relative levels of metabolites and bioenergetics between four melanoma models may produce differential therapeutic responses to BRAF inhibitors. Approach: Intratumor variations of lactate, alanine, and bioenergetics (β-NTP/Pi) measured by in-vivo and in-vitro 1H/31P MRS have the potential to become early and sensitive biomarkers of dabrafenib inhibition therapy in melanoma. Results: Changes in lactate, alanine, and bioenergetics response to targeted dabrafenib inhibitor therapy occur rapidly and are connected to the following tumor response. Impact: Dabrafenib blocks cell division by inhibiting the hyperactive BRAF protein. Differences in the predominance of metabolites (Lactate and Alanine) and bioenergetics may explain dabrafenib therapeutic responses in DB-1/WM983B (Sensitive mutant type), WM983BR (Resistant mutant type), and WM3918 (Wild type).