Natural and synthetic compounds targeting ferroptosis in esophageal squamous cell carcinoma: Research progress and application potential.

Esophageal Squamous Cell Carcinoma (ESCC) is a prevalent malignant tumor of the human digestive system, characterized by high incidence and mortality rates. Most patients are diagnosed at advanced stages, marked by metastasis and drug resistance, significantly limit the efficacy of conventional therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by dysregulated iron metabolism, lipid peroxidation, and compromised antioxidant defense system, has shown great potential in inhibiting the biological activity of cancer cells and improving prognosis. Thus, inducing ferroptosis could become a promising approach for cancer treatment. Bioactive small-molecule compounds, both natural and synthetic, offer unique advantages in the treatment of ESCC due to their distinct properties and potential efficacy. Modulating tumor cells survival via ferroptosis-whether through natural or synthetic agents-represents a crucial direction for precision ESCC therapy. In this review, we systematically outline the core mechanisms of ferroptosis and the roles of ferroptosis in ESCC. We also summarize a range of natural and synthetic compounds that target ferroptosis in ESCC cells, discussing their mechanisms of action and therapeutic potential. This review demonstrates that targeting ferroptosis with natural and synthetic compounds could be effective for ESCC treatments, and highlights a promising therapeutic avenue that could be utilized to prevent ESCC. This review article aims to shed light on developing novel therapeutic regimens by pharmacological induction of ferroptosis to treat ESCC efficiently in the future.