Cancers classified as multidrug-resistant (MDR) are a family of diseases with poor prognosis despite access to increasingly sophisticated treatments. Several mechanisms explain these resistances involving both tumor cells and their microenvironment. It is now recognized that a multi-targeting approach offers a promising strategy to treat these MDR tumors. Inhibition of thioredoxin reductase (TrxR), a key enzyme in maintaining redox balance in cells, is a well-identified target for this approach. Auranofin was the first inorganic gold complex to be described as a powerful inhibitor of TrxR. In this review, we will first recall the main results obtained with this metallodrug. Then, we will focus on organometallic complexes reported as TrxR inhibitors. These include gold(I), gold(III) complexes and metallocifens, i.e., organometallic complexes of Fe and Os derived from tamoxifen. In these families of complexes, similarities and differences in the molecular mechanisms of TrxR inhibition will be highlighted. Finally, the possible relationship between TrxR inhibition and cytotoxicity will be discussed and put into perspective with their mode of action.
被归类为多药耐药（MDR）的癌症是一类预后不良的疾病，尽管治疗方法日益精进。多种机制解释了这些耐药性，涉及肿瘤细胞及其微环境。目前公认，多靶点策略为治疗这类MDR肿瘤提供了有前景的途径。抑制硫氧还蛋白还原酶（TrxR）——一种维持细胞氧化还原平衡的关键酶，是该策略中已明确的重要靶点。金诺芬是首个被报道为强效TrxR抑制剂的无机金配合物。本综述将首先回顾该金属药物取得的主要研究成果，随后聚焦于已报道作为TrxR抑制剂的有机金属配合物，包括金(I)、金(III)配合物以及金属化他莫昔芬衍生物——即源自他莫昔芬的铁和锇有机金属配合物。在这些配合物家族中，我们将重点阐述其抑制TrxR分子机制的异同。最后，本文将探讨TrxR抑制与细胞毒性之间的潜在关联，并结合其作用机制进行前瞻性分析。
肿瘤(癌症)患者之家