Impact of non-genetic heterogeneity of BRAF-mutant colon cancer organoids on growth kinetics, drug sensitivity and Wnt dynamics - PubMed
6 hours ago
- #drug_sensitivity
- #organoid_heterogeneity
- #Wnt_pathway
- Patient-derived organoid (PDO) models retain genetic, histological, and functional characteristics of original tumors, aiding in studying tumor biology and drug response.
- Non-genetic parameters like organoid size, seeding density, and morphology influence proliferation, drug sensitivity, and Wnt responses in colorectal cancer organoids.
- Higher seeding density and larger organoid size reduce metabolic activity and decrease sensitivity to MEK inhibitor trametinib.
- Distinct morphological subgroups (solid vs. cystic organoids) show differential drug responses and Wnt-3a profiles under growth factor-deprived conditions.
- Solid organoids are more trametinib-sensitive and exhibit higher Wnt-3a levels, suggesting divergent cell compositions and pathway dependencies.
- Automated handling platforms improve reproducibility in organoid-based drug screening by controlling selection and screening conditions.