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Abstract #1146

Metabolic inhibition therapy targeting glutaminolysis in mantle cell lymphoma

Kavindra Nath1, Pradeep Kumar Gupta1, Shengchun Wang2, Shilpa Rao2, Alexander A. Shestov1, Neil Sen2, Stepan Orlovskiy1, Cosimo Lobello2, David Rushmore2, Johnvesly Basappa2, David S. Nelson1, Fernando Arias-Mendoza1,3, and Mariusz A. Wasik2
1University of Pennsylvania, Philadelphia, PA, United States, 2Fox Chase Cancer Center, Philadelphia, PA, United States, 3Advanced Imaging Research, Inc., Cleveland, OH, United States

Synopsis

Keywords: Biomarkers, Preclinical, Glutaminolysis, Mantle Cell Lymphoma Models, Early Metabolic Biomarker of Response, Proton MRS with Slice Selective Double Frequency Hadamard Selective Multiple Quantum Coherence Transfer Pulse Sequence

Motivation: Mantle cell lymphoma (MCL) poses clinical challenges due to resistance to current treatment modalities. Targeting cell metabolism may prove new therapeutic approach to MCL.

Goal(s): We evaluated effectiveness of CB-839, a glutaminase inhibitor, against MCL in in vitro and in vivo preclinical studies.

Approach: We employed 1H magnetic resonance spectroscopy (1H MRS) imaging and biochemical analyses to investigate the effects of CB-839 on key metabolites in MCL cells, to potentially identify biomarkers of treatment response.

Results: Decreases in lactate and alanine concentration emerged as promising biomarkers of response to CB-839 and may potentially serve as biomarkers in MCL patients.

Impact: Therapy-mediated decreased intra-tumoral concentrations of lactate and alanine measured by 1H MRS may potentially become early and sensitive biomarkers of glutaminase inhibition in MCL and, likely, other types of malignancies.

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