Ferroptosis-related small-molecule compounds in cancer therapy: Strategies and applications

Ferroptosis is a novel type of regulated cell death which is driven by iron-dependent lipid peroxidation and subsequent plasma membrane ruptures. Since ferroptosis was coined fairly in 2012, the research in the field of ferroptosis has grown at an exponential rate. Several small-molecule drugs have been shown to trigger ferroptosis and decrease tumor growth in the last decade. Sorafenib can induce ferroptosis in human hepatocellular car-cinoma cell lines (Huh7, Hep3B and HepG2), and sulfasalazine as a ferroptosis inducer can inhibit the prolif-eration of a series of cancer cell lines (including HT-1080 fibrosarcoma cells, Calu-1 non-small cell lung cancer cells, etc.) by specifically inhibit cystine transport which mediated by system Xc(-). The purpose of this review is discussing the current crosstalk between ferroptosis and tumor-related signaling pathways, as well as compre-hensively summarizing the small-molecule compounds that may regulate cancer cells death by inducing fer-roptosis which will shed new light on the development of ferroptosis-related anticancer drugs in the future.