Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China.
Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China.
Neoplasia. 2024 Sep;55:101017. doi: 10.1016/j.neo.2024.101017. Epub 2024 Jun 14.
Breast cancer (BC) is one of the primary causes of death in women worldwide. The challenges associated with adverse outcomes have increased significantly, and the identification of novel therapeutic targets has become increasingly urgent. Regulated cell death (RCD) refers to a type of cell death that can be regulated by several different biomacromolecules, which is distinctive from accidental cell death (ACD). In recent years, apoptosis, a representative RCD pathway, has gained significance as a target for BC medications. However, tumor cells exhibit avoidance of apoptosis and result in treatment resistance, which emphasizes further studies devoted to alternative cell death processes, namely necroptosis, pyroptosis, and ferroptosis. Here, in this review, we focus on summarizing the crucial signaling pathways of these RCD in BC. We further discuss the molecular mechanism and potentiality in clinical application of several prospective drugs, nanoparticles, and other small compounds targeting different RCD subroutines of BC. We also discuss the benefits of modulating RCD processes on drug resistance and the advantages of combining RCD modulators with conventional treatments in BC. This review will deepen our understanding of the relationship between RCD and BC, and shed new light on future directions to attack cancer vulnerabilities with RCD modulators for therapeutic purposes.
乳腺癌（BC）是全球女性死亡的主要原因之一。与不良预后相关的挑战显著增加，寻找新的治疗靶点变得日益紧迫。受调控的细胞死亡（RCD）是一种可被多种不同生物大分子调控的细胞死亡类型，与意外细胞死亡（ACD）不同。近年来，作为 BC 药物治疗靶点的代表性 RCD 途径——细胞凋亡备受关注。然而，肿瘤细胞逃避凋亡，导致治疗耐药性，这强调了进一步研究替代细胞死亡过程的必要性，即坏死性凋亡、细胞焦亡和铁死亡。在这篇综述中，我们重点总结了 RCD 在 BC 中的关键信号通路。我们进一步讨论了针对 BC 不同 RCD 亚类的几种有前途的药物、纳米颗粒和其他小分子的分子机制和临床应用潜力。我们还讨论了调节 RCD 过程对耐药性的益处，以及将 RCD 调节剂与传统治疗相结合在 BC 中的优势。这篇综述将加深我们对 RCD 与 BC 之间关系的理解，并为利用 RCD 调节剂靶向癌症脆弱性以达到治疗目的提供新的思路。
