From molecular crosstalk to precision therapy: targeting ferroptosis and cuproptosis in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck region, where conventional therapies have limited efficacy and patients have poor prognosis. As newly identified metal ion-dependent programmed cell death modalities, ferroptosis and cuproptosis play critical roles in tumor metabolism, immune microenvironment remodeling, and therapeutic resistance, representing emerging research foci in OSCC. This review examines the core molecular mechanisms of ferroptosis and cuproptosis and delineates their respective roles in OSCC initiation, progression, immune evasion, and therapeutic resistance. Furthermore, we explore the crosstalk between these two cell death modalities across oxidative stress, metabolic, and signaling networks. Synthesizing these findings, we outline emerging combination strategies that concurrently target ferroptosis and cuproptosis, and discuss current challenges and future directions for translating these concepts into precision therapies for OSCC.