Simultaneous Targeting of KRAS and CDK4 Synergistically Induces Durable Growth Arrest in Pancreatic Cancer Cells [51T-2D_RNA_Seq]

We report that the KRAS-G12C inhibitor Sotorasib synergizes with the CDK4/6 inhibitor Palbociclib to eliminate pancreatic ductal adenocarcinoma (PDAC) cells (51T-2D cells) harboring KRAS-G12C mutations. This synergy was especially pronounced following drug washout, indicating a durable cellular response. Mechanistically, the combinations induced sustained cell cycle arrest. Overall design: RNA-Sequencing of 51T-2D cells treated for 48 h with DMSO, Palbociclib (5 µM), Sotorasib (2.5 µM) or the combination (day3), or 48 h treatment + 4 days of recovery in normal cultivation medium (Day7).