Oncotarget

Research Perspectives:

Ferroptosis of epithelial ovarian cancer: genetic determinants and therapeutic potential

Chao-Chieh Lin and Jen-Tsan Chi _

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Oncotarget. 2020; 11:3562-3570. https://doi.org/10.18632/oncotarget.27749

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Abstract

Chao-Chieh Lin1,2 and Jen-Tsan Chi1,2

1 Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA

2 Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USA

Correspondence to:

Jen-Tsan Chi,email: jentsan.chi@duke.edu

Keywords: ferroptosis; cystine; ovarian cancer; GPX4; NADPH oxidase

Received: June 29, 2020     Accepted: August 26, 2020     Published: September 29, 2020

ABSTRACT

Epithelial ovarian cancer (OVCA) is the most lethal gynecologic cancer. Current treatment for OVCA involves surgical debulking of the tumors followed by combination chemotherapies. While most patients achieve complete remission, many OVCA will recur and develop chemo-resistance. Whereas recurrent OVCA may be treated by angiogenesis inhibitors, PARP inhibitors, or immunotherapies, the clinical outcomes of recurrence OVCA are still unsatisfactory. One new promising anti-tumor strategy is ferroptosis, a novel form of regulated cell death featured by lipid peroxidation. In this review, we have summarized several recent studies on the ferroptosis of OVCA. Also, we summarize our current understanding of various genetic determinants of ferroptosis and their underlying mechanisms in OVCA. Furthermore, ferroptosis can be combined with other standard cancer therapeutics, which has shown synergistic effects. Therefore, such a combination of therapeutics could lead to new therapeutic strategies to improve the response rate and overcome resistance. By understanding the genetic determinants and underlying mechanisms, ferroptosis may have significant therapeutic potential to improve the clinical outcome of women with OVCA.


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