Breast cancer (BC) is a heterogeneous cancer with multiple subtypes affecting women worldwide. Triple-negative breast cancer (TNBC) is a prominent subtype of BC with poor prognosis and an aggressive phenotype. Recent understanding of metabolic reprogramming supports its role in the growth of cancer cells and their adaptation to their microenvironment. The Warburg effect is characterized by the shift from oxidative to reductive metabolism and external secretion of lactate. The Warburg effect prevents the use of the required pyruvate in the tricarboxylic acid (TCA) cycle progressing through pyruvate dehydrogenase inactivation. Therefore, it is a major regulatory mechanism to promote glycolysis and disrupt the TCA cycle. Glutamine (Gln) can supply the complementary energy for cancer cells. Additionally, it is the main substrate to support bioenergetics and biosynthetic activities in cancer cells and plays a vital role in a wide array of other processes such as ferroptosis. Thus, the switching of glucose to Gln in the TCA cycle toward reductive Gln metabolism is carried out by hypoxia-inducible factors (HIFs) conducted through the Warburg effect. The literature suggests that the addiction of TNBC to Gln could facilitate the proliferation and invasiveness of these cancers. Thus, Gln metabolism inhibitors, such as CB-839, could be applied to manage the carcinogenic properties of TNBC. Such inhibitors, along with conventional chemotherapy agents, can potentially improve the efficiency and efficacy of TNBC treatment. In this review, we discuss the associations between glucose and Gln metabolism and control of cancer cell growth from the perspective that Gln metabolism inhibitors could improve the current chemotherapy drug effects.

中文翻译：

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与谷氨酰胺代谢相关的通路、谷氨酰胺抑制剂及其对提高三阴性乳腺癌化疗效率的影响。

乳腺癌 (BC) 是一种异质性癌症，具有多种亚型，影响着全世界的女性。三阴性乳腺癌 (TNBC) 是 BC 的一个突出亚型，预后差且具有侵袭性表型。最近对代谢重编程的理解支持其在癌细胞生长及其对微环境的适应中的作用。Warburg 效应的特点是乳酸从氧化代谢转变为还原代谢和外部分泌。Warburg 效应阻止在通过丙酮酸脱氢酶失活进行的三羧酸 (TCA) 循环中使用所需的丙酮酸。因此，它是促进糖酵解和破坏 TCA 循环的主要调节机制。谷氨酰胺（Gln）可以为癌细胞提供补充能量。此外，它是支持癌细胞中生物能量学和生物合成活动的主要底物，并在大量其他过程（如铁死亡）中发挥着至关重要的作用。因此，在 TCA 循环中葡萄糖向 Gln 向还原性 Gln 代谢的转换是通过 Warburg 效应进行的缺氧诱导因子 (HIF) 进行的。文献表明 TNBC 对 Gln 的成瘾可以促进这些癌症的增殖和侵袭。因此，Gln 代谢抑制剂，如 CB-839，可用于控制 TNBC 的致癌特性。此类抑制剂与常规化疗药物一起，可以潜在地提高 TNBC 治疗的效率和功效。在这次审查中，