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When combined with a PER2-activating agent, this strategy further enhances antitumor efficacy through synergistic cuproptosis induction ( As an emerging oncotherapeutic strategy, cuproptosis-directed therapy holds broad promise for OSCC, and future exploration should therefore reach beyond ionophores and nanomedicines to encompass systematic mining of natural-product libraries for plant-derived cuproptosis inducers, structure-based design of next-generation agents that selectively engage FDX1, DLAT or ATP7B, and rational integration of cuproptosis activators with radiation or cisplatin so as to override canonical resistance pathways

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Huh-Lunet-T7 RC cells were kindly provided by Prof