N-acetylcysteine (NAC) is a widely used antioxidant with therapeutic potential. However, the cancer-promoting effect of NAC observed in some preclinical studies has raised concerns regarding its clinical use. Reactive oxygen species (ROS) can mediate signaling that results in both cancer-promoting and cancer-suppressing effects. The beneficial effect of NAC may depend on whether the type of cancer relies on ROS signaling for its survival and metastasis. Triple-negative breast cancer (TNBC) has aggressive phenotypes and is currently treated with standard chemotherapy as the main systemic treatment option. Particularly, basal-like TNBC cells characterized by inactivated BRCA1 and mutated TP53 produce high ROS levels and rely on ROS signaling for their survival and malignant progression. In addition, the high ROS levels in TNBC cells can mediate the interplay between cancer cells and the tissue microenvironment (TME) to trigger the recruitment and conversion of stromal cells and induce hypoxic responses, thus leading to the creation of cancer-supportive TMEs and increased cancer aggressiveness. However, NAC treatment effectively reduces the ROS production and ROS-mediated signaling that contribute to cell survival, metastasis, and drug resistance in TNBC cells. Therefore, the inclusion of NAC in standard chemotherapy could probably provide additional benefits for TNBC patients.

中文翻译：

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N-乙酰半胱氨酸治疗三阴性乳腺癌的可能有益作用

N-乙酰半胱氨酸（NAC）是一种广泛使用的具有治疗潜力的抗氧化剂。然而，一些临床前研究中观察到的 NAC 的促癌作用引起了人们对其临床应用的担忧。活性氧 (ROS) 可以介导信号传导，从而产生促癌和抑癌作用。NAC 的有益效果可能取决于癌症类型是否依赖 ROS 信号来维持其生存和转移。三阴性乳腺癌（TNBC）具有侵袭性表型，目前采用标准化疗作为主要的全身治疗选择。特别是，以失活的BRCA1和突变的TP53为特征的基底样 TNBC 细胞产生高 ROS 水平，并依赖 ROS 信号传导来维持其生存和恶性进展。此外，TNBC细胞中的高ROS水平可以介导癌细胞与组织微环境（TME）之间的相互作用，从而触发基质细胞的募集和转化并诱导缺氧反应，从而导致癌症支持性TME的产生并增加癌症的侵袭性。然而，NAC 治疗有效地减少了 ROS 的产生和 ROS 介导的信号传导，这些信号有助于 TNBC 细胞的细胞存活、转移和耐药性。因此，将 NAC 纳入标准化疗可能会给 TNBC 患者带来额外的益处。