Metabolic programs associated with GDSC2-inferred oxaliplatin sensitivity are favorably prognostic in gastric cancer: transcriptomic and single-cell evidence.

GDSC2-inferred oxaliplatin resistance in gastric cancer is linked to increased glycolytic and oxidative metabolic programs, with these features showing favorable or neutral prognostic associations.

• Why it matters: Understanding molecular features associated with oxaliplatin sensitivity is crucial for improving treatment strategies in gastric cancer, but current knowledge is incomplete and heterogeneous.
• What they did: A ridge-regression model trained on 396 cell lines was applied to 412 primary tumors to predict oxaliplatin response, with subsequent analyses of gene expression, immune scores, and single-cell localization, plus experimental validation in AGS cells.
• The result: Resistant-like tumors exhibited higher glycolysis and oxidative phosphorylation scores, which correlated with better or neutral survival outcomes, highlighting the complex relationship between metabolic programs, drug response, and prognosis.