GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316631/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316631GEOGSEfalseSpatially resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma.Pancreatic ductal adenocarcinoma (PDAC) exhibits profound molecular heterogeneity and poor prognosis, necessitating novel tailored therapies. The basal and classical subtypes - driven by glycolysis versus lipid metabolism - have distinct prognostic implications. We mapped PDAC molecular subtype heterogeneity, capturing spatially-resolved gene expression signatures and generating a comprehensive high-resolution dataset of 42,035 spatial spots. Subtype assignments were validated via multiplex immunofluorescence and quantitative analyses in patient-derived organoids. Our analysis resolved cancer cell signatures, deconvoluted intra-tumoral heterogeneity, and delineated a classical-to-basal trajectory. We identified metabolically ‘hot’, high-grade tumor niches characterized by concurrent enrichment of glycolysis and lipogenesis across both subtypes, nominating them as subtype-agnostic therapeutic targets. Preclinical models demonstrated that despite the basal subtype’s glycolysis dependence, both classical and basal tumors are susceptible to glycolysis inhibition. This work challenges the dogma of subtype-specific therapeutic silos and demonstrates highly adaptable energetic niches as reservoirs to drive tumor progression.2026/04/22GSE316631GSM9457173GSM9457174GSM945717524676316631Homo sapiens[41896850]