Decoding cancer metabolism: A pan-cancer proteomics perspective

Metabolic reprogramming is a hallmark of cancer, yet the extent to which metabolic alterations are shared or distinct across cancer types remains incompletely understood. Here, we performed a systematic reanalysis of large-scale proteomic datasets spanning 16 diverse human cancers to uncover global and tissue-specific patterns of metabolic dysregulation. We found a striking inverse correlation between baseline metabolic activity in matched normal tissues and the degree of metabolic rewiring in tumors, pointing to a context-dependent metabolic shift during oncogenesis. Our analysis reveals frequently upregulated glycosylation-related pathways across cancers, along with coordinated alterations in nucleotide, carbohydrate, amino acid, and coenzyme & cofactor metabolism that collectively support biosynthesis, maintain redox balance, and sustain oncogenic signaling. These changes enable cancer cells to proliferate rapidly, evade cell death, and adapt to fluctuating environmental conditions. Together, our findings delineate both conserved and lineage-specific features of tumor metabolism, providing a pan-cancer perspective that may aid in identifying selective metabolic vulnerabilities and guiding the development of targeted therapeutic strategies.