Regorafenib induces DNA damage and enhances PARP inhibitor efficacy in pancreatic ductal carcinoma.

ABSTRACT:

Background

There is increasing interest in enhancing the response of the PARP inhibitor olaparib, which is currently approved for pancreatic ductal adenocarcinoma (PDAC) patients with defects in DNA damage repair associated with germline BRCA1/2 mutations. Moreover, agents that can mimic these defects in the absence of germline BRCA1/2 mutations are an area of active research in hopes of increasing the number of patients eligible for treatment with PARP inhibitors. The extent to which regorafenib, an FDA-approved tyrosine kinase inhibitor, can be used to enhance the efficacy of PARP inhibitors in PDAC cells without known BRCA1/2 mutations remains to be investigated.

Methods

Comet assay, cell cycle analysis, western blotting, and immunofluorescent detection of H2AX^S139</

SUBMITTER: Pham TD 

PROVIDER: S-EPMC11662535 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature