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Nevertheless, the spatio\u2010temporal molecular dynamics of multiple tissues during cancer cachexia development remain elusive. Here, we present a comprehensive overview of the biological alterations and metabolic reprogramming of cancer cachexia across two species, 25 organs, and 3230 samples, by integrating transcriptomic, proteomic, and metabolomic profiles spanning different cachectic stages and sexual dimorphism. Using this cancer cachexia atlas (CCAtlas), we identified dysregulated tissues of cancer cachexia, including skeletal muscle, liver, and blood. We revealed coordinated metabolic reprogramming across tissues, including dysregulated amino acid metabolism and one\u2010carbon metabolism. Temporal profiling illustrated dynamic molecular signatures during cancer cachexia progression. The exacerbated inflammatory status in males potentially contributed to a more severe whole\u2010body wasting phenotype. The liver\u2010muscle crosstalk potentiated skeletal muscle atrophy through creatine deficiency via hepatic Gamt downregulation in the LLC model. Creatine supplementation and hepatic Gamt overexpression in the LLC model attenuated skeletal muscle wasting. Together, CCAtlas provides fundamental and systemic insights into multi\u2010omic molecular dynamics and metabolic rewiring of cancer cachexia from the perspective of tumor and\/or inter\u2010organ crosstalk across species.<\/jats:p>","DOI":"10.1002\/advs.77489","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:57Z","timestamp":1788930537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Multi\u2010Omic Mapping Reveals Liver\u2010Muscle Metabolic Crosstalk in Cancer Cachexia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4500-0456","authenticated-orcid":false,"given":"Zihan","family":"Tian","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"},{"name":"Frontiers Science Center for Cancer Integrative 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