A Promising Future of Ferroptosis in Tumor Therapy

Abstract

Currently, mechanisms and therapeutic approaches have been thoroughly studied in various prevalent malignant tumors, such as breast and lung cancer. However, there is inevitable tumor progression and drug resistance. Uncovering novel treatment strategies to inhibit tumor development is important. Ferroptosis, a form of cell death associated with iron and lipid peroxidation, has drawn extensive attention. In this paper, we reviewed the underlying mechanisms of ferroptosis (i.e., iron, glutathione, and lipid metabolism) and its role in various tumors (i.e., lung cancer, liver carcinoma, breast cancer, and pancreatic cancer). Moreover, we summarized ferroptosis-related anti-tumor drugs and emphasized the potential of combined treatment of anti-tumor drugs and radiotherapy in an effort to provide novel anti-tumor treatments.

Keywords: anti-tumor therapy; ferroptosis; glutathione; iron; nanoparticle; radiotherapy.

FIGURE 1

The regulatory mechanisms of ferroptosis-related drugs or genes. Sorafenib, sulfasalazine, erastin/analogs and p53 inhibit SLC7A11 to trigger ferroptosis. GPX4 is directly inhibited by (1S, 3R)-RSL3, F2N56, FINO2, HSPAS. NADPH–FSP1–CoQ10 ferroptosis surveillance pathway acts in parallel to the GPX4 pathway. Low-density, lipoprotein, Nanoparticles can regulate GSH to induce ferroptosis. H₂O₂/Fe₃O₄-PLGA nanosystem can regulate Fenton reaction to induce ferroptosis.