Summary
Published in Nature Communications (2022), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Betge, Johannes, et al. The drug-induced phenotypic landscape of colorectal cancer organoids
The drug-induced phenotypic landscape of colorectal cancer organoids
Research Overview
Patient-derived organoids mirror tissue and tumor biology, but their morphologies vary widely for reasons that were unclear, as was any link to treatment response. This study quantified the phenotypes of more than five million individual colorectal cancer organoids after treatment with over 500 small molecules, using high-throughput image-based profiling integrated with multi-omics modeling.
Two axes of morphological variation emerged: organoid size tracks IGF1 receptor signaling, and cystic versus solid architecture tracks LGR5-positive stemness. Treatment-induced morphology reflected viability and drug mechanism in interpretable ways — MEK inhibition drove cystic reorganization and raised LGR5 expression, while mTOR inhibition acted through the IGF1 receptor axis.
Key Discoveries
- Over 5 million colorectal cancer organoids profiled by imaging after >500 compound treatments
- Organoid size linked to IGF1 receptor signaling; cystic vs solid architecture linked to LGR5+ stemness
- MEK inhibition induced cystic reorganization and increased LGR5; morphology reflected drug mechanism
