细胞凋亡传统上被认为是化疗药物激活的所需细胞死亡途径，因为它具有受控和非炎症的性质。然而，最近发现的替代细胞死亡途径为癌症的免疫刺激治疗方法铺平了道路。铁死亡（依赖于铁）和铜死亡（依赖于铜）有望选择性靶向癌细胞并克服耐药性。铜离子载体和含铁纳米药物显示出作为单一药物和辅助治疗的临床治疗潜力。在这里，我们回顾了金属离子依赖性细胞死亡途径参与经典化疗药物（烷化剂、拓扑异构酶抑制剂、抗代谢物和有丝分裂纺锤体抑制剂）及其与铜死亡和铁死亡诱导剂组合的细胞毒性的最新证据，指出其使用的前景、优势和障碍。版权所有 © 2024。由 Elsevier B.V. 出版。

Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative cell death pathways have paved the way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) and cuproptosis (dependent on copper) hold promise for selective cancer cell targeting and overcoming drug resistance. Copper ionophores and iron-bearing nano-drugs show potential for clinical therapy as single agents and as adjuvant treatments. Here we review up-to-date evidence for the involvement of metal ion-dependent cell death pathways in the cytotoxicity of classical chemotherapeutic agents (alkylating agents, topoisomerase inhibitors, antimetabolites, and mitotic spindle inhibitors) and their combinations with cuproptosis and ferroptosis inducers, indicating the prospects, advantages, and obstacles of their use.Copyright © 2024. Published by Elsevier B.V.