MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.

ABSTRACT:

Background

Although the clinical application of PARP inhibitors has brought hope to ovarian cancer, the problem of its resistance has become increasingly prominent. Therefore, clinical experts have been focused on finding specific indicators and therapeutic targets that can be used for resistance monitoring of PARP inhibitors.

Results

By cfDNA detecting during Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer, we found the presence of MRE11:p.K464R mutation was strongly associated with acquired Olaparib resistance. Structural analysis revealed that the MRE11:p.K464R mutation is situated at a critical site where the MRE11 protein interacts with other biomolecules, leading to potential structural and functional abnormalities of MRE11 protein. Functiona

SUBMITTER: Zhuang X 

PROVIDER: S-EPMC10537967 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature