Review Article Updates of the role of oxidative stress in the pathogenesis of ovarian cancer Ghassan M. Saed a, ⁎, Michael P. Diamond b , Nicole M. Fletcher a a The Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States b The Department of Obstetrics and Gynecology, Augusta University, Augusta, GA, United States HIGHLIGHTS • Oxidative stress plays an essential role in the pathogenesis of ovarian cancer. • Modulating the redox balance may have therapeutic value. • Chemoresistant ovarian cancer cells have an even further elevated oxidative stress. • Chemotherapy-induced mutations in redox enzymes may contribute to chemoresistance. abstract article info Article history: Received 31 December 2016 Received in revised form 16 February 2017 Accepted 20 February 2017 Available online 23 February 2017 Clinical and epidemiological investigations have provided evidence supporting the role of reactive oxygen spe- cies (ROS) and reactive nitrogen species (RNS), collectively known as oxidative stress, in the etiology of cancer. Exogenous factors such as chronic inflammation, infection and hypoxia are major sources of cellular oxidative stress. Specifically, oxidative stress plays an important role in the pathogenesis, neoangiogenesis, and dissemina- tion of local or distant ovarian cancer, as it is known to induce phenotypic modifications of tumor cells by cross talk between tumor cells and the surrounding stroma. Subsequently, the biological significance of the relation- ship between oxidative stress markers and various stages of epithelial ovarian cancer highlights potential thera- peutic interventions as well as provides urgently needed early detection biomarkers. In the light of our scientific research and the most recent experimental and clinical observations, this review provides the reader with up to date most relevant findings on the role of oxidative stress in the pathogenesis of ovarian cancer and the possible therapeutic implications. © 2017 Elsevier Inc. All rights reserved. Keywords: Ovarian cancer Oxidative stress Chemoresistance Genetic mutations Hypoxia Single nucleotide polymorphisms Contents 1. Ovarian cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596 2. Oxidative stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596 3. Oxidative stress and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596 4. Cancer cells are under intrinsic oxidative stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597 5. Ovarian cancer cells manifest a persistent pro-oxidant state . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598 6. Oxidative stress triggers cancer cells to favor anaerobic metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598 7. Chemotherapy and the acquisition of chemoresistance in EOC cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599 8. Polymorphisms in key oxidant and antioxidant enzymes are associated with ovarian cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 600 9. Acquisition of chemoresistance in ovarian cancer cells is associated with specific point mutations in key redox enzymes . . . . . . . . . . . . . 600 10. Ovarian cancer immunotherapy and oxidative stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 11. Summary and conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 Gynecologic Oncology 145 (2017) 595–602 ⁎ Corresponding author at: Wayne State University, 275 E Hancock Street, Detroit, MI 48201, United States. E-mail address: gsaed@med.wayne.edu (G.M. Saed). http://dx.doi.org/10.1016/j.ygyno.2017.02.033 0090-8258/© 2017 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno