Mitotic MTH1 inhibitor karonudib kills epithelial ovarian cancer independent of platinum sensitivity.

ABSTRACT: The prognosis for women with ovarian cancer (OC) is particularly poor if resistance to platinum compounds, the mainstay of standard-of-care therapy, develops. Inhibitors of the Nudix hydrolase MuT Homolog 1 (MTH1) have previously been shown to arrest cancer cells in mitosis, increase 8-oxo-2'-deoxyguanosine (8-oxo-dG) incorporation into DNA, and selectively kill neoplastic cells while sparing normal cells. Here we explored the cytotoxic mechanism of these agents as well as their activity against platinum-resistant OC in vitro and in vivo. Two mitotic MTH1 inhibitors (mMTH1is), TH588 and karonudib, decreased colony formation indistinguishably in platinum-sensitive OC cell lines and their platinum-resistant counterparts in vitro but had limited effects on fallopian tube and immortalized ovar

SUBMITTER: Hurley RM 

PROVIDER: S-EPMC12183885 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature