Extended Data Fig. 8. In vivo validation of combined targeting of irinotecan and CHEK1 in colon cancer.
a, Addition of rabusertib increases irinotecan response in two of three colon cancer xenograft models. NOD/scid mice were engrafted with colon cancer cell lines and treated with irinotecan (25 mg/kg twice a week) +/- rabusertib (200 mg/kg daily) for 24–35 days. Shown is average tumour volume change under treatment. LS-1034: n = 6 mice for vehicle, n = 11 for irinotecan, n = 12 for rabusertib and irinotecan+rabusertib. SW837: n = 6 mice for vehicle and rabusertib, n = 8 for irinotecan, n = 4 for irinotecan+rabusertib. SNU-81: n = 5 mice for vehicle and irinotecan+rabusertib, n = 6 for rabusertib, n = 10 for irinotecan. Two-way ANOVA. b, Treatment of rabusertib with irinotecan decreases proliferation. LS-1034 cells were engrafted and treated as described in (a). Tumours were collected 72 h after treatment start and stained for Ki67 (proliferative cells). n = 30 for vehicle, rabusertib and irinotecan+rabusertib; n = 25 for irinotecan. Mean ± SD. Two-tailed unpaired Welch’s t-test.