Iron-Dependent Cell Death: Exploring Ferroptosis as a Unique Target in Triple-Negative Breast Cancer Management

Li-kuan Tan,1 Jiaxing Liu,1 Cheng-zhi Ma,1 Shaolong Huang,1 Feng-hui He,1 Yang Long,1 Zhi-sheng Zheng,1 Jia-liang Liang,1 Nan Xu,1 Guanghui Wang,2 Yu-fei Liu1 1Breast Surgery, Tongren People’s Hospital, Tongren, People’s Republic of China; 2Breast Surgery, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of ChinaCorrespondence: Guanghui Wang; Yu-fei Liu, Email [email protected]; [email protected]: Triple-negative breast cancer (TNBC) is characterized by aggressive behavior, high metastatic potential, and frequent relapses, presenting significant treatment challenges. Ferroptosis, a unique form of programmed cell death marked by iron-dependent lipid peroxidation, has emerged as a crucial factor in cancer biology. Recent studies indicate that TNBC cells possess a distinct metabolic profile linked to iron and glutathione, which may render them more susceptible to ferroptosis than other breast cancer subtypes. Moreover, ferroptosis plays a role in the interactions between immune cells and tumor cells, suggesting its potential to modulate the tumor microenvironment and influence the immune response against TNBC.Evidence reveals that ferroptosis not only affects TNBC cell viability but also alters the tumor microenvironment by promoting the release of damage-associated molecular patterns (DAMPs), which can recruit immune cells to the tumor site. Specific ferroptosis-related genes and biomarkers, such as ACSL4 and GPX4, demonstrate altered expression patterns in TNBC tissues, offering promising avenues for diagnostic and prognostic applications. Furthermore, in preclinical models, the induction of ferroptosis has been shown to enhance the efficacy of existing therapies, indicating a synergistic effect that could be harnessed for therapeutic benefit. The compelling link between ferroptosis and TNBC underscores its potential as a novel therapeutic target. Future research should focus on developing strategies that exploit ferroptosis in conjunction with traditional therapies, including the identification of natural compounds and efficacious ferroptosis inducers for personalized treatment regimens. This review elucidates the multifaceted implications of ferroptosis in TNBC, providing valuable insights for improving both diagnosis and treatment of this formidable breast cancer subtype.Keywords: triple-negative breast cancer, ferroptosis, programmed cell death, immune response, therapeutic strategies