Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer.

ABSTRACT:

Purpose

Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.

Materials and methods

We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.

Results

In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olap

SUBMITTER: Seo HR 

PROVIDER: S-EPMC9016294 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature