Genes differentially affected by CDK4/6 inhibitor and KRAS inhibitor

We are trying to expand the usage of CDK4/6 inhibitors to non-breast solid tumors, however, most clinical trials with its single-use failed to advance to higher stages. CDK4/6 inhibitors induce cellular senescence in pancreatic cancer cells. In an aim to find drug that may enhance the efficacy of therapy with CDK4/6 inhibitors, we screened compound libraries and found inhibitors to EGFR/MEK/ERK pathway are promising. We further discovered that CDK4/6 inhibitor downregulates KRAS activity in KRAS mutated pancreatic cancer cells however upregulates ERK and MEK activity. To determine how KRAS downregulation contributes to induction of cellular senescence in pancreatic cancer cells, we treated MIA PaCa-2 cells with 1 uM Sotorasib or 10 uM Palbociclib for 72 hrs. The data we uploaded contain RNA sequence results of differentially-treated MIA PaCa-2 cells.