MTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to CHK1 Inhibitors in Ewing Sarcoma Cells.

ABSTRACT: The treatment of Ewing sarcoma has changed very little in the past two decades and novel treatment approaches are needed. We recently identified that Ewing sarcoma cells are uniquely vulnerable to inhibitors of ribonucleotide reductase (RNR), the rate-limiting enzyme in the synthesis of deoxyribonucleotides. We subsequently found that the inhibition of checkpoint kinase 1 (CHK1) increases the sensitivity of Ewing sarcoma cells to inhibitors of RNR, such as gemcitabine. However, Ewing sarcoma cells exhibit high levels of the CHK1 protein, which may represent an adaptive response to elevated levels of endogenous DNA replication stress. Consequently, we began this work with the aim of determining the impact of CHK1 levels on drug sensitivity, as well as identifying the mechanisms and pathways

SUBMITTER: Koppenhafer SL 

PROVIDER: S-EPMC6279492 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature