Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Assessment of Metabolic Imaging Biomarkers for MEK Inhibition Therapy Response in Melanoma

Version 1 : Received: 19 June 2024 / Approved: 19 June 2024 / Online: 19 June 2024 (14:19:34 CEST)

How to cite: Gupta, P. K.; Orlovskiy, S.; Arias-Mendoza, F.; Nelson, D. S.; Nath, K. Assessment of Metabolic Imaging Biomarkers for MEK Inhibition Therapy Response in Melanoma. Preprints 2024, 2024061354. https://doi.org/10.20944/preprints202406.1354.v1 Gupta, P. K.; Orlovskiy, S.; Arias-Mendoza, F.; Nelson, D. S.; Nath, K. Assessment of Metabolic Imaging Biomarkers for MEK Inhibition Therapy Response in Melanoma. Preprints 2024, 2024061354. https://doi.org/10.20944/preprints202406.1354.v1

Abstract

The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine of melanoma patients. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels at early stages of effective therapy and could be construed as metabolic imaging biomarkers for drug response. The present work aimed to demonstrate if these metabolic changes and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for early predicting melanoma response to MEK inhibition.

Keywords

melanoma; trametinib; 1H/31P magnetic resonance spectroscopy; oxygen consumption rate; extracellular acidification rate; glucose uptake; lactate production.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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