Emerging mechanisms and targeted therapy of ferroptosis in cancer

• Published in: Molecular therapy Vol. 29; no. 7; pp. 2185 - 2208
• Main Authors: Wang, Haiyan, Cheng, Yan, Mao, Chao, Liu, Shuang, Xiao, Desheng, Huang, Jun, Tao, Yongguang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.07.2021; American Society of Gene & Cell Therapy
• Subjects: Animals; Antineoplastic Agents - therapeutic use; cancer suppressor; cancer therapy; Ferroptosis; ferroptosis-related proteins; Humans; iron; lipid ROS; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Review; Tumor Microenvironment; cancer therapy; iron; ferroptosis; ferroptosis-related proteins; lipid ROS; cancer suppressor
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1016/j.ymthe.2021.03.022

Ferroptosis is an iron- and lipid reactive oxygen species (ROS)-dependent form of programmed cell death that is distinct from other forms of regulatory cell death at the morphological, biological, and genetic levels. Emerging evidence suggests critical roles for ferroptosis in cell metabolism, the redox status, and various diseases, such as cancers, nervous system diseases, and ischemia-reperfusion injury, with ferroptosis-related proteins. Ferroptosis is inhibited in diverse cancer types and functions as a dynamic tumor suppressor in cancer development, indicating that the regulation of ferroptosis can be utilized as an interventional target for tumor treatment. Small molecules and nanomaterials that reprogram cancer cells to undergo ferroptosis are considered effective drugs for cancer therapy. Here, we systematically summarize the molecular basis of ferroptosis, the suppressive effect of ferroptosis on tumors, the effect of ferroptosis on cellular metabolism and the tumor microenvironment (TME), and ferroptosis-inducing agents for tumor therapeutics. An understanding of the latest progress in ferroptosis could provide references for proposing new potential targets for the treatment of cancers. [Display omitted] Ferroptosis, an iron- and lipid ROS-dependent form of programmed cell death, plays critical roles in killing cancer cells. Herein, we summarize the effect of ferroptosis on cellular metabolism and the tumor microenvironment and ferroptosis inducers for tumor therapeutics. This review could provide references for targeting ferroptosis in tumor treatment.