Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance

To assess whether Selumetinib-treated colorectal cancer cells escape G1 cell cycle arrest using incorporation assays for the thymidine analogue 5- ethynyl 2-deoxyuridine (EdU) and to characterise cells that undergo DNA replication during short-term and/or prolonged treatment with Selumetinib Conclusion: Selumetinib causes G1 cell cycle arrest, but cells occasionally enter the cell cycle and initiate DNA replication despite robust G1 cell cycle arrest induced by the drug. Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies Appropriate control cell populations were included for each assay. For each EdU incorporation assay, control cells that were unstained for EdU and underwent the same incubation and washing steps were used