Neuron-gastric tumor organoid reveals metabolic vulnerabilities in gastric cancer
Organoid and immortalized cell line cultures for cancer target discovery show discrepancies.
The researchers in this study use CRISPR screens in patient-derived tumor organoids to reveal metabolic vulnerabilities not seen in 2D and 3D spheroid models and identify potent inhibitors that target gastric cancer’s lipid metabolism. The authors show that enteric neurons modulate lipid metabolism in tumor organoids, altering drug sensitivity by up to two orders of magnitude.
The authors identify lanosterol synthase and acetyl-coenzyme A (CoA) carboxylase inhibitors as effective treatments that impede xenografted tumor growth in mice.
A neuron-cancer coculture screen found that ACC level predicts treatment efficacy, highlighting neuronal interaction in cancer lipid reliance.
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(25)00298-X
