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 FDX1 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 FDX1 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 in vitro and in vivo across diverse cancer models. In this review, we summarize the regulatory mechanisms governing FDX1 expression and its functional roles in cancer progression. We also highlight its potential as a therapeutic target in cancer therapy.