A combined enteric neuron-gastric tumor organoid reveals metabolic vulnerabilities in gastric cancer

作者：Becky K.C. Chan, Chu Zhang, Chi Him Poon, M. Lee, Hoi Yee Chu, Bei Wang, Sin-Guang Chen, Helen H.N. Yan, Suet Yi Leung, Alan S.L. Wong · 发表于：Cell stem cell · 年份：2025 · DOI：10.1016/j.stem.2025.08.006 · 被引用次数：13 · 研究领域：Diet and metabolism studies、Cancer, Hypoxia, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response

) values across diverse human gastric cancer organoids resistant to first-line treatments. Mechanistically, gastric cancer organoids and in vivo tumors exhibit lipid metabolic adaptations not seen in two-dimensional (2D) in vitro cultures. Additionally, enteric neurons modulate lipid metabolism in tumor organoids, altering drug sensitivity by up to two orders of magnitude. A neuron-cocultured CRISPR screen further reveals that acetyl-CoA carboxylase expression determines lanosterol synthase inhibitor efficacy. These findings highlight the critical roles of organoid environment and neuronal interaction in cancer lipid reliance.