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脂肪酸的合成是乳腺癌脑转移所必需的

原文发布日期：2021-04-01

英文摘要：

摘要翻译：

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脂肪酸的合成是乳腺癌脑转移所必需的

Fatty acid synthesis is required for breast cancer brain metastasis

原文发布日期：2021-04-01

英文摘要：

Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive 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 the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.

摘要翻译：

脑转移性乳腺癌患者EGFR阳性时，系统性疾病治疗效果不佳，而大脑微环境可能与这种治疗耐药有关。营养素在不同组织中的可用性可能不同，因此需要考虑代谢适应对治疗的潜在影响。接下来是具体的研究内容：评估脑转移和非脑转移乳腺癌肿瘤的代谢差异，发现脑转移肿瘤中脂肪酸合成增加。推测这是因脑部脂质供应减少而发生的特定适应性。最后，研究显示抑制脂肪酸合成了体外抑制脑转移性EGFR阳性的乳腺癌生长，证明不同转移部位的营养素差异导致可靶向的代谢依赖。