University of Lodz, Faculty of Biology and Environmental Protection, Department of Molecular Biotechnology and Genetics, Banacha St. 12/16, 90-237 Lodz, Poland.
University of Lodz, Faculty of Biology and Environmental Protection, Department of Molecular Biotechnology and Genetics, Banacha St. 12/16, 90-237 Lodz, Poland; University of Lodz, Doctoral School of Exact and Natural Sciences, Banacha Street 12/16, 90-237 Lodz, Poland.
Biochim Biophys Acta Rev Cancer. 2024 Jul;1879(4):189124. doi: 10.1016/j.bbcan.2024.189124. Epub 2024 May 25.
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.
细胞凋亡一直被认为是化疗药物激活的理想细胞死亡途径，因为它具有可控性和非炎症性。然而，最近对其他细胞死亡途径的发现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）有望实现选择性的癌细胞靶向和克服耐药性。铜载体和含铁纳米药物作为单药和辅助治疗具有临床治疗的潜力。在这里，我们综述了最新的证据，证明金属离子依赖性细胞死亡途径参与了经典化疗药物（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）的细胞毒性作用，以及它们与铜死亡和铁死亡诱导剂的联合作用，表明了它们的使用前景、优势和障碍。
