Junfeng Zhang: Writing – original draft. Jianyou Gu: Writing – review & editing, Writing – original draft, Visualization, Supervision, Conceptualization.

No conflict of interest exists in the submission of this manuscript. We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled. We certify that the submission is not under review by any other

This work was sponsored by the National Natural Science Foundation of China (No. 82203165) and Graduate Research and Innovation Foundation of Chongqing, China (No. CYB25071) for Jianyou Gu. The authors gratefully acknowledge Prof. Huaizhi Wang and Prof. Shixiang Guo (Chongqing General Hospital, Chongqing University) for constructive suggestions.

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Hepatocellular and pancreatic cancers are highly aggressive malignancies with dismal clinical outcomes, highlighting an urgent need for new therapeutic strategies. Magnesium-related alloys, widely explored for their biocompatibility and bioactivity, are attractive candidates for biliary and pancreatic duct stents. However, their antitumor potential and underlying mechanisms remain incompletely defined. Here, we systematically characterized the physicochemical properties and anticancer activities of a panel of magnesium-related alloy powders and identified an aluminum-magnesium (Al-Mg) alloy as the most potent candidate. Compared with pure Mg, Al-Mg rods exhibited stronger antitumor efficacy together with more controllable degradation. In vitro and in vivo assays confirmed that Al-Mg significantly inhibited hepatocellular carcinoma and pancreatic cancer progression. Integrated metabolomic and transcriptomic analyses indicated that Al-Mg activates AMPK signaling and suppresses purine and pyrimidine metabolism, consistent with metabolic reprogramming that limits tumor cell proliferation. Furthermore, single-cell and spatial transcriptomic analyses delineated Al-Mg-sensitive tumor cell subpopulations and mapped their spatial distribution within pancreatic cancer tissues. Collectively, these findings position Al-Mg as a promising antitumor material and provide a mechanistic framework supporting the development of magnesium-related alloys for local oncologic intervention.

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