Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer.

ABSTRACT:

Purpose

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.

Materials and methods

We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings.

Results

In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed ant

SUBMITTER: Jin MH 

PROVIDER: S-EPMC6962488 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature