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Metrics details. Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK, and the mechanisms involved in the schedule dependence. Growth inhibition induced by gemcitabine plus MK was assessed across multiple cancer cell lines. We assessed the effect of different treatment schedules on cell cycle perturbation and tumor cell growth in vitro and in xenograft tumor models. MK induced an average 7-fold sensitization to gemcitabine in 16 cancer cell lines. The time of MK administration significantly affected the response of tumor cells to gemcitabine.
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Study record managers: refer to the Data Element Definitions if submitting registration or results information. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 courses in the absence of disease progression or unacceptable toxicity. Mean NAR scores along with standard errors and confidence intervals will be reported by treatment.