(A), Lovo cell line xenografts were treated with vehicle control daily, palbociclib 100 mg/kg daily, trametinib 3 mg/kg every 2 days, or palbociclib 100 mg/kg daily + trametinib 3 mg/kg every 2 days, and tumor volume was measured twice per week. Data are mean ± SEM, with 10 mice/arm. *p < 0.01 on day 21 for combination vs. each other arm by Student's t-test. (B), HCT116 cell line xenografts were treated with control chow or chow containing trametinib + palbociclib, and tumor volume was measured longitudinally. ♦p < 0.001 on day 7 by Student's t-test. (C), SW480 cell line xenografts were treated with control chow or chow containing trametinib + palbociclib, and tumor volume was measured longitudinally. ♦p < 0.001 on day 20 by Student's t-test. (D), Xenografts implanted with patient-derived CRC cells harboring KRAS A146T mutation were treated with vehicle control daily, palbociclib 100 mg/kg daily, trametinib 3 mg/kg every 2 days, or palbociclib 100 mg/kg daily + trametinib 3 mg/kg every 2 days, and tumor volume was measured twice per week. Data are mean ± SEM, with 9–10 mice/arm. ♦p < 0.001 on day 21 for combination vs. any other arm by Student's t-test. Dotted lines represent 50% decrease in tumor volume. (E), Change in tumor volume for each of the patient-derived xenograft mice in D at day 21 of treatment.