Targeting ferroptosis as a vulnerability in cancer

被引:1591
作者
Lei, Guang [1 ]
Zhuang, Li [1 ]
Gan, Boyi [1 ,2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; CELL-DEATH; TUMOR-SUPPRESSOR; LIPID-PEROXIDATION; PROMOTES FERROPTOSIS; SYNTHETIC LETHALITY; TRANSPORT ACTIVITY; NUCLEAR FORM; METABOLISM; PATHWAY;
D O I
10.1038/s41568-022-00459-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ferroptosis is an iron-dependent form of regulated cell death that is triggered by the toxic build-up of lipid peroxides on cellular membranes. In recent years, ferroptosis has garnered enormous interest in cancer research communities, partly because it is a unique cell death modality that is mechanistically and morphologically different from other forms of cell death, such as apoptosis, and therefore holds great potential for cancer therapy. In this Review, we summarize the current understanding of ferroptosis-inducing and ferroptosis defence mechanisms, dissect the roles and mechanisms of ferroptosis in tumour suppression and tumour immunity, conceptualize the diverse vulnerabilities of cancer cells to ferroptosis, and explore therapeutic strategies for targeting ferroptosis in cancer. In recent years, research in the field of ferroptosis in cancer has risen steeply in part owing to its potential to be targeted. In this Review, Lei et al. provide an up-to-date synthesis of the roles and mechanisms of ferroptosis in tumour growth and progression, including its function in tumour immunity, highlighting it as a vulnerability that can be exploited for cancer therapy.
引用
收藏
页码:381 / 396
页数:16
相关论文
共 202 条
[21]   NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression [J].
Chen, Delin ;
Tavana, Omid ;
Chu, Bo ;
Erber, Luke ;
Chen, Yue ;
Baer, Richard ;
Gu, Wei .
MOLECULAR CELL, 2017, 68 (01) :224-+
[22]   Iron Metabolism in Ferroptosis [J].
Chen, Xin ;
Yu, Chunhua ;
Kang, Rui ;
Tang, Daolin .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8
[23]   ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway [J].
Chu, Bo ;
Kon, Ning ;
Chen, Delin ;
Li, Tongyuan ;
Liu, Tong ;
Jiang, Le ;
Song, Shujuan ;
Tavana, Omid ;
Gu, Wei .
NATURE CELL BIOLOGY, 2019, 21 (05) :579-+
[24]   Comprehensive molecular profiling of lung adenocarcinoma [J].
Collisson, Eric A. ;
Campbell, Joshua D. ;
Brooks, Angela N. ;
Berger, Alice H. ;
Lee, William ;
Chmielecki, Juliann ;
Beer, David G. ;
Cope, Leslie ;
Creighton, Chad J. ;
Danilova, Ludmila ;
Ding, Li ;
Getz, Gad ;
Hammerman, Peter S. ;
Hayes, D. Neil ;
Hernandez, Bryan ;
Herman, James G. ;
Heymach, John V. ;
Jurisica, Igor ;
Kucherlapati, Raju ;
Kwiatkowski, David ;
Ladanyi, Marc ;
Robertson, Gordon ;
Schultz, Nikolaus ;
Shen, Ronglai ;
Sinha, Rileen ;
Sougnez, Carrie ;
Tsao, Ming-Sound ;
Travis, William D. ;
Weinstein, John N. ;
Wigle, Dennis A. ;
Wilkerson, Matthew D. ;
Chu, Andy ;
Cherniack, Andrew D. ;
Hadjipanayis, Angela ;
Rosenberg, Mara ;
Weisenberger, Daniel J. ;
Laird, Peter W. ;
Radenbaugh, Amie ;
Ma, Singer ;
Stuart, Joshua M. ;
Byers, Lauren Averett ;
Baylin, Stephen B. ;
Govindan, Ramaswamy ;
Meyerson, Matthew ;
Rosenberg, Mara ;
Gabriel, Stacey B. ;
Cibulskis, Kristian ;
Sougnez, Carrie ;
Kim, Jaegil ;
Stewart, Chip .
NATURE, 2014, 511 (7511) :543-550
[25]   The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability [J].
Conrad, M ;
Moreno, SG ;
Sinowatz, F ;
Ursini, F ;
Kölle, S ;
Roveri, A ;
Brielmeier, M ;
Wurst, W ;
Maiorino, M ;
Bornkamm, GW .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (17) :7637-7644
[26]   The chemical basis of ferroptosis [J].
Conrad, Marcus ;
Pratt, Derek A. .
NATURE CHEMICAL BIOLOGY, 2019, 15 (12) :1137-1147
[27]   Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth [J].
Cramer, Shiro L. ;
Saha, Achinto ;
Liu, Jinyun ;
Tadi, Surendar ;
Tiziani, Stefano ;
Yan, Wupeng ;
Triplett, Kendra ;
Lamb, Candice ;
Alters, Susan E. ;
Rowlinson, Scott ;
Zhang, Yan Jessie ;
Keating, Michael J. ;
Huang, Peng ;
DiGiovanni, John ;
Georgiou, George ;
Stone, Everett .
NATURE MEDICINE, 2017, 23 (01) :120-127
[28]   Discovery of ubiquinone (coenzyme Q) and an overview of function [J].
Crane, Frederick L. .
MITOCHONDRION, 2007, 7 :S2-S7
[29]   Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis [J].
Cui, Weiwei ;
Liu, Dong ;
Gu, Wei ;
Chu, Bo .
CELL DEATH AND DIFFERENTIATION, 2021, 28 (08) :2536-2551
[30]   NRF2 and the Hallmarks of Cancer [J].
de la Vega, Montserrat Rojo ;
Chapman, Eli ;
Zhang, Donna D. .
CANCER CELL, 2018, 34 (01) :21-43