alexa Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Timmerman LA, Holton T, Yuneva M, Louie RJ, Padr M,

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Abstract A handful of tumor-derived cell lines form the mainstay of cancer therapeutic development, yielding drugs with an impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics and more readily understand their clinical impact, we constructed a functional metabolic portrait of 46 independently derived breast cell lines. Our analysis of glutamine uptake and dependence identified a subset of triple-negative samples that are glutamine auxotrophs. Ambient glutamine indirectly supports environmental cystine acquisition via the xCT antiporter, which is expressed on one-third of triple-negative tumors in vivo. xCT inhibition with the clinically approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development. Copyright © 2013 Elsevier Inc. All rights reserved.
This article was published in Cancer Cell and referenced in Journal of Clinical & Experimental Pharmacology

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