Products Cited in Publications Worldwide Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma

Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma

Gupta, Pradeep Kumar; Orlovskiy, Stepan; Arias-Mendoza, Fernando; Nelson, David S.; Osborne, Aria; Pickup, Stephen; Glickson, Jerry D.; Nath, Kavindra

DOI: PMID:

Abstract

therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (1H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (1H/31P) MRS. We found consistent changes in lactate and , either in isolated cells or mouse xenografts, correlating with their relative responsiveness. In xenografts, we also observed that a more significant response to correlated with higher bioenergetics (i.e., increased βNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by 1H/31P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under and probably other signaling inhibition therapies.

Keywords

BRAF ; cancer biomarkers ; ; magnetic resonance spectroscopy ; melanoma ; response prediction

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