Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer

Feifei Pu; Fengxia Chen; Zhicai Zhang; Deyao Shi; Binlong Zhong; Xiao Lv; Andrew Blake Tucker; Jiaming Fan; Alexander J Li; Kevin Qin; Daniel Hu; Connie Chen; Hao Wang; Fang He; Na Ni; Linjuan Huang; Qing Liu; William Wagstaff; Hue H Luu; Rex C Haydon; Le Shen; Tong-Chuan He; Jianxiang Liu; Zengwu Shao

doi:10.1016/j.gendis.2020.11.019

Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer

Genes Dis. 2020 Dec 4;9(2):347-357. doi: 10.1016/j.gendis.2020.11.019. eCollection 2022 Mar.

Authors

Feifei Pu¹, Fengxia Chen^{2

3}, Zhicai Zhang¹, Deyao Shi^{1

4}, Binlong Zhong¹, Xiao Lv^{1

5}, Andrew Blake Tucker⁴, Jiaming Fan^{4

6}, Alexander J Li⁴, Kevin Qin⁴, Daniel Hu⁴, Connie Chen⁴, Hao Wang^{4

6}, Fang He^{4

7}, Na Ni^{4

6}, Linjuan Huang^{4

7}, Qing Liu^{4

8}, William Wagstaff⁴, Hue H Luu⁴, Rex C Haydon⁴, Le Shen^{4

9}, Tong-Chuan He^{4

9}, Jianxiang Liu¹, Zengwu Shao¹

Affiliations

¹ Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
² Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, PR China.
³ Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, PR China.
⁴ Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
⁵ Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21205, USA.
⁶ Ministry of Education Key Laboratory of Diagnostic Medicine, Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, PR China.
⁷ Departments of Nephrology, and Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
⁸ Department of Spine Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
⁹ Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.

Abstract

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

Keywords: Cancer; Cancer therapy; Clinical application; Ferroptosis; Lipid peroxidation; Pathogenesis.

Publication types

Review