Exploring SPK98 for the Selective Sensitization of ATM- or P53-Deficient Cancer Cells.

ABSTRACT: Frequent mutation in the ATM/P53 signaling pathway has been documented in many human cancers. Reportedly, cancer cells with deficient P53/ATM pathways depend on functional Ataxia-telangiectasia and Rad3-related (ATR) protein for survival. This has prompted research in developing ATR inhibitors for the selective sensitization of cancer cells that are P53/ATM-deficient, but no clinical success has been attained thus far. This study explores the therapeutic potential of SPK98, an analogue of Torin2 in P53- and ATM-deficient cancer cells. Furthermore, the prospect of improving the therapeutic outcome of the genotoxic agent was also explored. SPK98 was shown to inhibit full-length human ATR protein purified from HEK293T cells. Cellular investigation using SPK98 demonstrated that it selectively

SUBMITTER: Priya B 

PROVIDER: S-EPMC9909806 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature