Targeted therapy combinations with ipatasertib in multi-cell type 3D tumor spheroid models.

ABSTRACT: We investigated the growth-inhibitory activity of the pan-AKT inhibitor ipatasertib in combination with other targeted therapies. Thirty-nine patient-derived cancer cell lines from the NCI Patient-Derived Models Repository and nine NCI-60 tumor cell lines were grown as mct-spheroids. The mct-spheroids, a mixture of tumor cells (60%), endothelial cells (25%), and mesenchymal stem cells (15%), were established for 3 days before compounds(s) were added. All agents were tested at concentrations up to the reported clinical C_max values or a high concentration of 10 μM. Cell viability was assayed using CellTiter-Glo 3D after 7 days of exposure. Ipatasertib was selective for tumor cells harboring activating PI3K/AKT/mTOR pathway mutations. Dual inhibition of the PI3K/AKT/mTOR and RAS/ME

SUBMITTER: Teicher BA 

PROVIDER: S-EPMC12320941 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature