Colorectal Cancer Organoid Model Reveals the Mechanisms of Irinotecan Resistance at Single‐Cell Resolution

This study integrates PDO models with single-cell transcriptomics technology to reveal key cell subpopulations and molecular mechanisms underlying irinotecan resistance. The core mechanisms driving resistance involve the activation of Wnt signaling and the synergistic effect of lipid metabolism-Notch pathways. Cluster 1 and Cluster 6 are identified as potential therapeutic targets, providing a theoretical basis for developing combination therapies targeting cancer stem cells or the metabolic microenvironment.