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Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target

Timmerman, LA and Holton, T and Yuneva, M and Louie, RJ and Padro, M and Daemen, A and Hu, M and Chan, DA and Ethier, SP and van 't Veer, LJ and Polyak, K and McCormick, F and Gray, JW (2013) Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target. CANCER CELL. pp. 450-465.

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

Item Type: Article
Additional Information: pubid: 107 nvp_institute: NIBR contributor_address: Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA timmerma@cc.ucsf.edu; San Francisco State Univ, Sch Engn, San Francisco, CA 94115 USA ; MRC Natl Inst Med Res, Div Physiol & Metab, London NW7 1AA, England ; Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA, Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94115 USA ; Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA, Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94115 USA ; Novartis Inst BioMed Res China, Pudong New Area, Shanghai 201203, Peoples R China ; Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA ; Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA ; Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA ; Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA; Timmerman, LA; Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21945

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