Ferroptosis in biliary tract cancer: Molecular mechanisms and therapeutic applications (Review)

Biliary tract cancer (BTC) encompasses a group of aggressive malignancies arising from the bile duct epithelium, including gallbladder cancer and cholangiocarcinoma, which are characterized by aggressive progression, frequent metastases and poor prognoses. BTC accounts for ~3% of all digestive system tumors, with a 5‑year overall survival rate of <20%. BTC presents a clinical challenge. Despite multidisciplinary therapeutic approaches incorporating surgery, chemotherapy and radiotherapy, persistent obstacles, including high tumor recurrence rates (>50%) and the development of treatment resistance remains, underscoring the urgent need for novel treatment strategies such as targeted therapies and immunotherapies. Ferroptosis, a distinct mechanism of regulated cell death triggered by lipid peroxidation, serves critical roles in disease occurrence and progression. Increasing evidence supports the potential of ferroptosis as a targeted therapy in malignancies, with emerging implications for personalized BTC treatment. The present review investigated the molecular mechanisms and signaling pathways that govern ferroptosis, the advances in the understanding of ferroptosis during the initiation and progression of BTC, and the translation potential of ferroptosis for precision therapeutics. By integrating current knowledge, the present study aimed to provide theoretical suggestions for future mechanistic investigations and clinical studies of ferroptosis‑based interventions for patients with BTC.