Transcriptomic changes of NECC organoids after Quisinostat 2HCl treatment

Organoid-based high-throughput screening (HTS) is revolutionizing pharmaceutical development. However, the complexity of handling extracellular matrix (ECM) components with traditional HTS devices leads to the use of suspension cultures for organoids during HTS. To address the limitations in suspended organoid-based HTS, we developed a whole-process 3D ECM-encapsulated organoid-based automated HTS (wp3D-OAHTS) platform. Using this platform, we conducted a 3D organoid-based HTS of 2,802 small molecules against neuroendocrine cervical cancer (NECC) organoids, and identified Quisinostat 2HCl as a promising therapeutic candidate for NECC. Further, we examined the principal transcriptomic changes in NECC organoids after treatment with Quisinostat 2HCl, and revealed significant downregulation in multiple metabolic pathways such as cholesterol metabolism, steroid synthesis, and glycolysis/gluconeogenesis in Quisinostat 2HCl-treated organoids. This finding suggests that Quisinostat 2HCl might inhibit the growth of NECC organoids by metabolism reprogramming