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Inhibition of CHK1 sensitizes Ewing sarcoma cells to the ribonucleotide reductase inhibitor gemcitabine.
In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR. However, clofarabine is a reversible inhibitor of RNR and we found that the effect of clofarabine is limited when using a short (6-hour) drug treatment. Gemcitabine, on the other hand, is an irreversible inhibitor of the RRM1 subunit of RNR and this drug induces apoptosis in Ewing sarcoma cells when used in both 6-hour and longer drug treatments. Treatment of Ewing sarcoma cells with gemcitabine also results in activation of checkpoint kinase 1 (CHK1), which is a crit...
Source: Oncotarget - November 22, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MLN-8237; A dual inhibitor of aurora A and B in soft tissue sarcomas.
Authors: Nair JS, Schwartz GK Abstract Aurora kinases have become an attractive target in cancer therapy due to their deregulated expression in human tumors. Liposarcoma, a type of soft tissue sarcoma in adults, account for approximately 20% of all adult soft tissue sarcomas. There are no effective chemotherapies for majority of these tumors. Efforts made to define the molecular basis of liposarcomas lead to the finding that besides the amplifications of CDK4 and MDM2, Aurora Kinase A, also was shown to be overexpressed. Based on these as well as mathematic modeling, we have carried out a successful preclinical stu...
Source: Oncotarget - February 19, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research