Circular Rnas in Ferroptosis Regulation and Tumor Progression of Gynecological and Breast Cancers: Molecular Mechanisms and Therapeutic Potential Publisher Pubmed

Summary: Can tumor cell death be controlled through circular RNA? A review suggests circRNA–ferroptosis may offer targets, but trials are lacking. #Ferroptosis #CancerResearch

Hushmandi K ; Mirnejad A M ; Bemidinezhad A ; Nejati H ; Ghaderi M ; Tavassoli Razavi F ; Doosti P ; Mafi A ; Alimohammadi M ; Farahani N
Source: Clinical and Translational Oncology Published:2026

Abstract

Ferroptosis is a distinct form of regulated cell death that is characterized by iron-dependent oxidative damage and the excessive accumulation of lipid peroxides within cellular membranes. Increasing evidence indicates that ferroptosis is closely associated with tumor initiation, progression, metastasis, and resistance to anticancer therapies. This form of cell death has consequently attracted considerable attention as a potential therapeutic mechanism in a range of malignancies, particularly breast and gynecological cancers. Circular RNAs (circRNAs) are a diverse group of non-coding RNA molecules distinguished by their covalently closed circular structures and remarkable stability. Accumulating evidence has established circRNAs as important regulators of cancer-associated molecular processes at the post-transcriptional level. In the context of ferroptosis, circRNAs may modulate cellular susceptibility to oxidative cell death through several mechanisms, including sequestration of microRNAs, interactions with RNA-binding proteins, and regulation of signaling networks and genes involved in iron metabolism, lipid homeostasis, antioxidant defense, and redox balance. This review provides an overview of the fundamental molecular mechanisms underlying ferroptosis and examines the emerging roles of circRNAs in regulating ferroptotic responses across breast, ovarian, cervical, and endometrial cancers. Particular emphasis is placed on the molecular interactions through which circRNAs influence ferroptosis-associated pathways and on their potential utility as diagnostic, prognostic, and therapeutic biomarkers. The interplay between circRNAs and ferroptosis represents an important area of cancer research, because it may provide new insights into tumor biology and reveal previously unexplored opportunities for precision therapeutic intervention. Nevertheless, further mechanistic investigations, comprehensive in vivo studies, and well-designed clinical investigations are required to establish the translational relevance of these findings and determine whether circRNA–ferroptosis regulatory networks can be effectively exploited in clinical oncology. © The Author(s), under exclusive licence to Federacion de Sociedades Espanolas de Oncologia (FESEO) 2026.