In vivo response of TNBC tumors to agents that target CHK1, RRM1 and RRM2. (A) SCID mice with MDA-MB-231 tumor xenografts were treated seven days after implantation with vehicle, 5 mg/kg gemcitabine, 6 mg/kg UCN-01, or a combination of both on a Q4Dx3 schedule. Gemcitabine was delivered first by IP injection and UCN-01 was delivered 24 hours later by IV injection on a Q6Hx2. Note: Inset graph highlights days 7 to 21. During this period, mice treated with the combination therapy had slower growing tumors than those treated only with gemcitabine. (B) SCID mice with C3(1)Tag tumor transplants were dosed 12 days after transplantation with 20 mg/kg gemcitabine, 4.5 mg/kg UCN-01, or the drug combination on a Q4Dx3 schedule. Gemcitabine was delivered first and UCN-01 was delivered eight hours later on a Q6Hx2 schedule.