Co-targeting ferroptosis and immune evasion through small molecules in breast cancer

Abstract Breast cancer accounts for the highest proportion of cancer cases among women worldwide. Despite remarkable advances in cancer diagnosis and treatment, novel precision therapy strategies for various subtypes of breast cancer are urgently needed. Ferroptosis, which is different from programmed cell death, such as apoptosis, necrosis, and pyroptosis, is considered an alternative method for cancer therapy. A comprehensive understanding of ferroptosis in breast cancer is lacking, including, but not limited to, ferroptotic inducers (small molecule drugs and natural products) and the interaction between ferroptosis and immunotherapy. Induction of ferroptosis is recognized as a novel and promising strategy for cancer pharmacotherapy, and a comprehensive understanding of the role of ferroptosis in breast cancer could help provide alternative treatment strategies for breast cancer. Furthermore, we highlight the signaling crosstalk bridging ferroptosis with the immune microenvironment and the feasibility of targeting their potential regulators ( e.g ., STAT3, AR, EZH2, and PRMT5) using small molecules to simultaneously achieve the induction of ferroptosis and inhibition of immune escape.