Targeting ferroptosis in renal cell carcinoma: Potential mechanisms and novel therapeutics

Renal cell carcinoma (RCC) is an increasingly prevalent urologic malignancy that impacts human health worldwide. Surgery is an effective strategy for early RCC treatment, but advanced RCC is resistant to chemotherapy, thus development of other potential therapeutic strategies is urgent. Ferroptosis is a newly defined form of programmed cell death characterized by accumulation of iron-dependent lipid peroxides and plays a crucial role in the tumor progression and drug resistance. Recent studies have shown that ferroptosis participates in RCC progression and chemoresistance. Therefore, identifying the potential role of ferroptosis in RCC could develop novel therapeutic targets and clinical markers for this disease. This review concisely summarizes the regulatory role of iron, amino acid, and lipid metabolism in ferroptosis, as well as discusses the relationship between ferroptosis and RCC, and details the role of ferroptosis in tumor progression, which indicates that various ferroptosis regulators are dysregulated in RCC and exert paradoxical effects, either tumor-suppressive or oncogenic. These ferroptosis-related regulators are expected to be used as clinical markers for RCC prognosis. Thus, targeting these regulators to trigger ferroptosis may be the key to the development of potential therapeutic strategies for this disease.