| Literature DB >> 34179825 |
Gino B Ferraro1, Ahmed Ali2,3, Alba Luengo2,4, David P Kodack1,5, Amy Deik3, Keene L Abbott2,4, Divya Bezwada1, Landry Blanc6,7, Brendan Prideaux6,8, Xin Jin3, Jessica M Posada1,9, Jiang Chen1, Christopher R Chin2, Zohreh Amoozgar1, Raphael Ferreira2,10, Ivy X Chen1, Kamila Naxerova1,11, Christopher Ng2, Anna M Westermark2, Mark Duquette1, Sylvie Roberge1, Neal I Lindeman9, Costas A Lyssiotis12,13, Jens Nielsen10, David E Housman2,4, Dan G Duda1, Elena Brachtel14, Todd R Golub3, Lewis C Cantley12,15, John M Asara12, Shawn M Davidson2,3,4,16, Dai Fukumura1, Véronique A Dartois6,17, Clary B Clish3, Rakesh K Jain18, Matthew G Vander Heiden19,20,21,22.
Abstract
Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain. We determine that this phenotype is an adaptation to decreased lipid availability in brain relative to other tissues, resulting in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.Entities:
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Year: 2021 PMID： 34179825 PMCID： PMC8223728 DOI： 10.1038/s43018-021-00183-y
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347