The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

SIMPLE SUMMARY: Despite decades of extensive study into targeting cell death in breast cancer, including apoptosis, the clinical treatment remains challenging due to its high probability of recurrence. As an emerging form of cell death, ferroptosis features suppression of drug resistance and augmentation of antitumor immunity. The advances in the development of clinical drugs targeting ferroptosis provide growing silver linings for breast cancer treatment. Research into biomarkers to precisely trace ferroptosis in patients with cancer, and the development and subsequent application of novel ferroptosis-based therapies will be of critical importance in the next few years. ABSTRACT: Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.