Department of Pharmacology and Therapeutics, Center for Genetics & Pharmacology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cells. 2019 Jan 26;8(2):89. doi: 10.3390/cells8020089.
Current standard-of-care (SOC) therapy for breast cancer includes targeted therapies such as endocrine therapy for estrogen receptor-alpha (ERα) positive; anti-HER2 monoclonal antibodies for human epidermal growth factor receptor-2 (HER2)-enriched; and general chemotherapy for triple negative breast cancer (TNBC) subtypes. These therapies frequently fail due to acquired or inherent resistance. Altered metabolism has been recognized as one of the major mechanisms underlying therapeutic resistance. There are several cues that dictate metabolic reprogramming that also account for the tumors' metabolic plasticity. For metabolic therapy to be efficacious there is a need to understand the metabolic underpinnings of the different subtypes of breast cancer as well as the role the SOC treatments play in targeting the metabolic phenotype. Understanding the mechanism will allow us to identify potential therapeutic vulnerabilities. There are some very interesting questions being tackled by researchers today as they pertain to altered metabolism in breast cancer. What are the metabolic differences between the different subtypes of breast cancer? Do cancer cells have a metabolic pathway preference based on the site and stage of metastasis? How do the cell-intrinsic and -extrinsic cues dictate the metabolic phenotype? How do the nucleus and mitochondria coordinately regulate metabolism? How does sensitivity or resistance to SOC affect metabolic reprogramming and vice-versa? This review addresses these issues along with the latest updates in the field of breast cancer metabolism.
目前乳腺癌的标准治疗（SOC）包括针对雌激素受体-α（ERα）阳性的内分泌治疗；针对人表皮生长因子受体-2（HER2）富集的抗 HER2 单克隆抗体；以及针对三阴性乳腺癌（TNBC）亚型的一般化疗。这些治疗方法经常因获得性或固有耐药而失败。代谢改变已被认为是治疗耐药的主要机制之一。有几个线索可以决定代谢重编程，这也解释了肿瘤的代谢可塑性。为了使代谢疗法有效，有必要了解不同类型乳腺癌的代谢基础，以及 SOC 治疗在靶向代谢表型方面的作用。了解其机制将使我们能够确定潜在的治疗弱点。今天的研究人员正在解决一些与乳腺癌代谢改变相关的非常有趣的问题。不同类型乳腺癌之间的代谢差异是什么？癌细胞是否根据转移部位和阶段对代谢途径有偏好？细胞内和细胞外线索如何决定代谢表型？核和线粒体如何协调调节代谢？SOC 的敏感性或耐药性如何影响代谢重编程，反之亦然？本文综述了这些问题以及乳腺癌代谢领域的最新进展。
