乳腺癌（BC）是女性癌症死亡的主要原因。这种疾病是异质性的，临床亚型有雌激素受体-α（ER-α）阳性、人表皮生长因子受体2（HER2）过表达或ER-α、孕激素受体和HER2（TNBC）三阴性。对于ER-α阳性和HER2过表达的肿瘤可以使用针对这些蛋白质的药物进行治疗，包括他莫昔芬和帕珥嘱单抗。尽管有这些治疗方法，但药物抗性和转移问题仍然存在。而由于缺乏适当的目标，治疗TNBC则十分具有挑战性。许多研究表明N-myc下游调控基因-1（NDRG1）在转移抑制方面在BC和其他肿瘤中发挥重要作用。NDRG1抑制转移的能力部分归因于抑制转移的初始步骤，即上皮细胞-间充质细胞转化。然而，有反向报道显示NDRG1在BC发病中也起着促癌作用。NDRG1在BC的致癌作用与脂质代谢或mTOR信号通路有关。NDRG1是如何调节多条信号通路的作用机制尚不明确。开发上调NDRG1的治疗策略，包括二-吡啶酮硫代卡巴肼类化合物。这些化合物可针对BC细胞的致癌驱动因子进行靶向，抑制多种关键激素受体的表达，包括ER-α、孕激素受体、雄激素受体和催乳素受体，还可以克服他莫昔芬耐药。考虑到NDRG1在BC发病中的不同作用，需要进一步研究哪类BC患者可以从上调NDRG1的药物中获益。 Copyright © 2023. Elsevier B.V.出版。

Breast cancer (BC) is the leading cause of cancer death in women. This disease is heterogeneous, with clinical subtypes being estrogen receptor-α (ER-α) positive, having human epidermal growth factor receptor 2 (HER2) overexpression, or being triple-negative for ER-α, progesterone receptor, and HER2 (TNBC). The ER-α positive and HER2 overexpressing tumors can be treated with agents targeting these proteins, including tamoxifen and pertuzumab, respectively. Despite these treatments, resistance and metastasis are problematic, while TNBC is challenging to treat due to the lack of suitable targets. Many studies examining BC and other tumors indicate a role for N-myc downstream-regulated gene-1 (NDRG1) as a metastasis suppressor. The ability of NDRG1 to inhibit metastasis is due, in part, to the inhibition of the initial step in metastasis, namely the epithelial-to-mesenchymal transition. Paradoxically, there are also reports of NDRG1 playing a pro-oncogenic role in BC pathogenesis. The oncogenic effects of NDRG1 in BC have been reported to relate to lipid metabolism or the mTOR signaling pathway. The molecular mechanism(s) of how NDRG1 regulates the activity of multiple signaling pathways remains unclear. Therapeutic strategies that up-regulate NDRG1 have been developed and include agents of the di-2-pyridylketone thiosemicarbazone class. These compounds target oncogenic drivers in BC cells, suppressing the expression of multiple key hormone receptors including ER-α, progesterone receptor, androgen receptor, and prolactin receptor, and can also overcome tamoxifen resistance. Considering the varying role of NDRG1 in BC pathogenesis, further studies are required to examine what subset of BC patients would benefit from pharmacopeia that up-regulate NDRG1.Copyright © 2023. Published by Elsevier B.V.