乳腺癌
转移
脑转移
内科学
癌症研究
医学
乳腺癌转移
癌症
肿瘤科
癌症转移
作者
Gino B. Ferraro,Ahmed Ali,Alba Luengo,David P. Kodack,Amy Deik,Keene L. Abbott,Divya Bezwada,Landry Blanc,Brendan Prideaux,Xin Jin,Jessica M. Posada,Jiang Chen,Christopher R. Chin,Zohreh Amoozgar,Raphaël Ferreira,Ivy X. Chen,Kamila Naxerova,Christopher Ng,Anna M. Westermark,Mark Duquette
出处
期刊:Nature cancer
[Springer Nature]
日期:2021-04-01
卷期号:2 (4): 414-428
被引量:303
标识
DOI:10.1038/s43018-021-00183-y
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI