A mini-review and perspective on ferroptosis-inducing strategies in cancer therapy

• Published in: Chinese chemical letters 2019-04, Vol.30 (4), p.847-852
• Main Authors: Wang, Shuaifei, Liao, Hongwei, Li, Fangyuan, Ling, Daishun
• Format: Article
• Language: English
• Subjects: Fenton reaction; Ferroptosis; Glutathione peroxidase 4; Lipid peroxidation; Reactive oxygen species
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2019.03.025

This review summarizes recent advances and challenges in ferroptosis-based anticancer strategies through Fenton reaction or GPX4 inactivation, with highlights on nanomaterials and perspectives on future development of next-generation ferroptosis-inducing agents based on diverse polyvalent metals. [Display omitted] Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic potential as a target for cancer therapy. Hitherto, there are mainly two strategies widely adopted for designing ferroptosis-inducing agents, which include increasing the intracellular reactive oxygen species (ROS) level by Fenton reaction, and inactivating the glutathione peroxidase 4 (GPX4). In this mini-review, we summarize the recent advances in ferroptosis-based anticancer treatments with a highlight on nanomaterials, and discuss the current challenges faced by those agents from the perspective of in vivo applications. Moreover, by generalizing ferroptosis induced by excess iron ions to cell death caused by the polyvalent metal-mediated oxidative burden, we introduce a new paradigm of cancer treatment by exploiting various polyvalent metals to disrupt the vulnerable redox balance in cancer cells, which may greatly diversify our arsenal to combat cancer.