Branched Organoids Reveal Phenotype-Specific Vulnerabilities in Pancreatic Cancer

A study published in Nature Biomedical Engineering demonstrates that novel branched-organoid models of pancreatic ductal adenocarcinoma (PDAC) effectively mimic the significant intratumoral and intertumoral heterogeneity observed in human and mouse tumors—characteristics often missed by conventional organoid methods. These organoids, cultured within collagen gels, revealed distinct tumor-cell states driven primarily by epithelial-to-mesenchymal plasticity, each exhibiting unique molecular, morphological, and therapeutic response profiles. Importantly, the researchers created phenotypic heterogeneity maps identifying specific vulnerabilities and therapy-induced phenotype shifts. This approach opens new avenues for phenotype-targeted therapies and personalized treatment strategies to combat PDAC chemoresistance.