Difluoromethylornithine (DFMO) Enhances the Cytotoxicity of PARP Inhibition in Ovarian Cancer Cells.

ABSTRACT: Ovarian cancer accounts for 3% of the total cancers in women, yet it is the fifth leading cause of cancer deaths among women. The BRCA1/2 germline and somatic mutations confer a deficiency of the homologous recombination (HR) repair pathway. Inhibitors of poly (ADP-ribose) polymerase (PARP), another important component of DNA damage repair, are somewhat effective in BRCA1/2 mutant tumors. However, ovarian cancers often reacquire functional BRCA and develop resistance to PARP inhibitors. Polyamines have been reported to facilitate the DNA damage repair functions of PARP. Given the elevated levels of polyamines in tumors, we hypothesized that treatment with the polyamine synthesis inhibitor, α-difluoromethylornithine (DFMO), may enhance ovarian tumor sensitivity to the PARP inhibitor, rucapa

SUBMITTER: El Naggar O 

PROVIDER: S-EPMC9230675 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature