Targeting ferroptosis: a promising avenue for Ovarian Cancer treatment 1

Xiaolan Wu^1,2,3Qizhi Liu⁴Zhili Jiang⁵Guiyun Wang¹Lingyu Liao¹Xiaojuan Ye¹Min Xing¹Han Sun¹Qiying Liu^6*Huiping Liu^1*

• ¹School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, Changsha, China
• ²Hunan Provincial Key Laboratory of Traditional Chinese Medicine Prescription and Syndrome Differentiation Translational Medicine, Changsha, Hunan 410007, People’s Republic of China, Changsha, China
• ³The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410021, People’s Republic of China, Changsha, China
• ⁴College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, People’s Republic of China., Changsha, China
• ⁵Medical School of Hunan University of Chinese Medicine, Changsha, Hunan 410208, People’s Republic of China, Changsha, China
• ⁶Changsha Hospital for Maternal and Child Health Care, Changsha, Hunan410008,People’s Republic of China, Changsha, China

Ovarian cancer(OC) is the second most common gynecological malignancy worldwide. While traditional treatments such as cytoreductive surgery, chemotherapy, and targeted drugs have made progress, patients with advanced disease still face high recurrence rates and resistance to treatment. As a result, there is an urgent need to develop new therapeutic strategies. Ferroptosis, a novel form of programmed cell death characterized by iron-dependent lipid peroxidation, has recently gained attention for its potential in cancer therapy. Studies indicate that OC cells are highly sensitive to ferroptosis, and targeting this pathway can effectively overcome chemotherapy resistance and improve treatment outcomes. This review systematically examines the molecular mechanisms of ferroptosis and its role in OC, with a focus on its involvement in tumor initiation, progression, TME and resistance. Furthermore, we highlight the research advancements on various ferroptosis inducers, including natural products, small molecule compounds, and nanotechnology, and explore their potential in overcoming resistance and enhancing patient prognosis. We also discuss the challenges facing ferroptosis-based treatments for OC, such as species differences, drug resistance, personalized treatment needs, and clinical translation issues.Ultimately, targeted modulation of ferroptosis offers new hope for OC therapy.