Role of Ferredoxin 1 (FDX1) in cancer and its therapeutic potential

Ferredoxin 1 (FDX1) is a small iron-sulfur (Fe-S) cluster protein localized to the mitochondria. It functions as an electron carrier in diverse metabolic pathways and is critically involved in regulating protein lipoylation Accumulating evidence indicates that <i>FDX1</i> expression is frequently dysregulated across various cancer types. Its expression is significantly associated with cancer progression, prognosis, and tumor immune responses, suggesting its potential as a biomarker for cancer diagnosis, prognostic evaluation, and immunotherapy response prediction. Transcription factors, epigenetic modifications, and non-coding RNAs (ncRNAs) contribute to the aberrant expression of <i>FDX1</i> in cancer cells. Mechanistic studies reveal that FDX1 protein influences cancer progression by modulating oncogenic signaling pathways, metabolic reprogramming, and tumor immunity; Notably, FDX1 serves as a central mediator of cuproptosis - a copper-dependent form of programmed cell death - highlighting its potential tumor-suppressive function. Therefore, FDX1 may exert dual roles in cancer by either promoting or inhibiting disease progression. Recently, several agents targeting FDX1 have exhibited promising therapeutic efficacy both <i>in vitro</i> and <i>in vivo</i> across diverse cancer models. In this review, we summarize the regulatory mechanisms governing <i>FDX1</i> expression and its functional roles in cancer progression. We also highlight its potential as a therapeutic target in cancer therapy.