Affiliation:
1. Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Abstract
Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is largely lacking. In this review, we summarize the current understanding of ferroptosis-regulating mechanisms with respect to the metabolism of phospholipids and iron as well as major anti-oxidative pathways that protect cells from ferroptosis. We also highlight the diverse impact of p53, a master regulator of cell death and cellular metabolic processes, on the regulation of ferroptosis. Lastly, we discuss recent ferroptosis studies in leukemia and provide a future perspective for the development of promising anti-leukemia therapies implementing ferroptosis induction.
Funder
Relay For Life My Oncology Dream Award
Mochida Memorial Foundation for Medical and Pharmaceutical Research
Uehara Memorial Foundation Research Fellowship
MD Anderson Cancer Center Institutional Research
New Investigator Research Grant Program
NIH Leukemia SPORE Development Research Program
Start-up fund in MD Anderson Cancer Center
FDA R01
NIH
NIH STTR
MD Anderson MDS/AML Moon Shot Program
Paul & Mary Haas Chair in Genetics
NCI Cancer Center
Cited by
6 articles.
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