biostudies-literatureUnknownKpenu EKNCI NIH HHS<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly cancer with limited treatment options. The base excision repair (BER) pathway, crucial for fixing DNA abasic sites, is driven by apurinic/apyrimidinic endonuclease 1 (APE1). While APE1's redox function has been extensively studied, its endonuclease activity in PDAC homeostasis and therapeutic response remains poorly understood. We created stable, homozygous APE1 endonuclease-reduced PDAC cell lines to examine the effects of impaired BER activity on pancreatic cancer growth, progression, and response to treatment.<h4>Methods</h4>CRISPR/Cas9-mediated editing was used to introduce an E96A mutation into the Pa03C PDAC cell line, generating three clonal mutant cell lines: E96A B1, E96A B4, E96A G8. APE1 expression andResearch squarers.3.rs-8197122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12776480biostudies-literatureTargeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.PMC12776480R01 CA282478R01 CA254110P30 CA082709U01 CA274304Kelley MRHaiaty SPeil JWireman RSLiu SKpenu EKGampala SSharma AMijiti MSardar RFishel MLWan JMitchell DKGeorgiadis MMfalseTargeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly cancer with limited treatment options. The base excision repair (BER) pathway, crucial for fixing DNA abasic sites, is driven by apurinic/apyrimidinic endonuclease 1 (APE1). While APE1's redox function has been extensively studied, its endonuclease activity in PDAC homeostasis and therapeutic response remains poorly understood. We created stable, homozygous APE1 endonuclease-reduced PDAC cell lines to examine the effects of impaired BER activity on pancreatic cancer growth, progression, and response to treatment.<h4>Methods</h4>CRISPR/Cas9-mediated editing was used to introduce an E96A mutation into the Pa03C PDAC cell line, generating three clonal mutant cell lines: E96A B1, E96A B4, E96A G8. APE1 expression and2025-01-01T00:00:00Z2025 Dec2026-07-05T03:10:17.967Z2026-07-05T03:08:10.845ZS-EPMC127764804151022610.21203/rs.3.rs-8197122/v1