Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells.

ABSTRACT: The DNA-damage-activated checkpoint protein CHK1 is required to prevent replication or mitosis in the presence of unrepaired DNA damage. Inhibitors of CHK1 (CHK1i) circumvent this checkpoint and enhance cell killing by DNA-damaging drugs. CHK1i also elicit single-agent cytotoxicity in a small subset of cell lines. Resolving the mechanisms underlying the single-agent activity may permit patient stratification and targeted therapy against sensitive tumors. Our recent comparison of three CHK1i demonstrated that they all inhibited protein synthesis only in sensitive cells. LY2606368, the most selective of these CHK1i, was used in the current study. Comparison across a panel of cell lines demonstrated that sensitive cells died upon incubation with LY2606368, whereas resistant cells underwent gr

SUBMITTER: Hinds JW 

PROVIDER: S-EPMC8369673 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature