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Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

Pisarsky, Laura and Bill, Ruben and Fagiani, Ernesta and Dimeloe, Sarah and Goosen, Ryan William and Hagmann, Jörg and Hess, Christoph and Christofori, Gerhard. (2016) Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy. Cell Reports, 15 (6). pp. 1161-1174.

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Official URL: https://edoc.unibas.ch/61446/

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Abstract

Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO) efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C)
03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M. and Hess, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2211-1247
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Mar 2019 17:46
Deposited On:19 Mar 2019 17:46

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