癌症的特征是代谢重编程，这是肿瘤治疗研究的热门话题。癌细胞改变代谢途径以促进其生长，这些改变代谢途径的共同目的是适应癌细胞不受控制的增殖状态。大部分非低氧状态下的癌细胞将增加葡萄糖摄取并产生乳酸，称为华法林效应。增加的葡萄糖消耗被用作支持细胞增殖的碳源，包括核苷酸、脂质和蛋白质的合成。在华法林效应中，丙酮酸脱羧酶活性降低，从而破坏三羧酸循环。除了葡萄糖外，谷氨酰胺也是癌细胞生长和增殖的重要营养素，是癌细胞生长和增殖的重要碳库和氮库，提供对癌细胞生长和增殖所必需的核糖、非必需氨基酸、柠檬酸和甘油，同时弥补了华法林效应引起的癌细胞氧化磷酸化途径的减少。在人体血浆中，谷氨酰胺是最丰富的氨基酸。正常细胞通过谷氨酰胺合酶(GLS)合成谷氨酰胺，但肿瘤细胞合成的谷氨酰胺不足以满足其高增长需求，导致“依赖谷氨酰胺现象”。大多数癌症都有增加的谷氨酰胺需求，包括乳腺癌。代谢重编程不仅使肿瘤细胞能够维持氧化还原平衡并投入资源进行生物合成，而且确定了不同于非肿瘤细胞的异质代谢表型的肿瘤细胞。因此，针对肿瘤和非肿瘤细胞之间的代谢差异可能是一种有前途和新颖的抗癌策略。代谢重编程的谷氨酰胺代谢区已成为有前途的候选项，特别是在三阴性乳腺癌和耐药乳腺癌中。在这篇综述中，讨论了乳腺癌和谷氨酰胺代谢的最新发现，讨论了基于氨基酸转运蛋白和谷氨酰胺酶的新疗法，并解释了谷氨酰胺代谢和乳腺癌转移、耐药、肿瘤免疫和铁死亡之间的关系，为乳腺癌的临床治疗提供了新思路。版权所有©2023 Elsevier Inc. 发布。

Cancer is characterized by metabolic reprogramming, which is a hot topic in tumor treatment research. Cancer cells alter metabolic pathways to promote their growth, and the common purpose of these altered metabolic pathways is to adapt the metabolic state to the uncontrolled proliferation of cancer cells. Most cancer cells in a state of nonhypoxia will increase the uptake of glucose and produce lactate, called the Warburg effect. Increased glucose consumption is used as a carbon source to support cell proliferation, including nucleotide, lipid and protein synthesis. In the Warburg effect, pyruvate dehydrogenase activity decreases, thereby disrupting the TCA cycle. In addition to glucose, glutamine is also an important nutrient for the growth and proliferation of cancer cells, an important carbon bank and nitrogen bank for the growth and proliferation of cancer cells, providing ribose, nonessential amino acids, citrate, and glycerin necessary for cancer cell growth and proliferation and compensating for the reduction in oxidative phosphorylation pathways in cancer cells caused by the Warburg effect. In human plasma, glutamine is the most abundant amino acid. Normal cells produce glutamine via glutamine synthase (GLS), but the glutamine synthesized by tumor cells is insufficient to meet their high growth needs, resulting in a "glutamine-dependent phenomenon." Most cancers have an increased glutamine demand, including breast cancer. Metabolic reprogramming not only enables tumor cells to maintain the reduction-oxidation (redox) balance and commit resources to biosynthesis but also establishes heterogeneous metabolic phenotypes of tumor cells that are distinct from those of nontumor cells. Thus, targeting the metabolic differences between tumor and nontumor cells may be a promising and novel anticancer strategy. Glutamine metabolic compartments have emerged as promising candidates, especially in TNBC and drug-resistant breast cancer. In this review, the latest discoveries of breast cancer and glutamine metabolism are discussed, novel treatment methods based on amino acid transporters and glutaminase are discussed, and the relationship between glutamine metabolism and breast cancer metastasis, drug resistance, tumor immunity and ferroptosis are explained, which provides new ideas for the clinical treatment of breast cancer.Copyright © 2023. Published by Elsevier Inc.