CDK4 and neoplasm: Interestingly, when TR14 cells were treated with the CDK4/6 inhibitors abemaciclib, and to a greater extent palbociclib, a shift in the distribution of CDK4 ecDNA to higher copy number was detected in resistant tumor cells (Extended Data Figs. 7d,e and 8), which is consistent with previous reports across different tumors showing that high CDK4 copy number and expression promotes resistance to CDK4/6 inhibitors30.