Abstract 6968: Targeting overexpressed NEK2 kinase in esophageal adenocarcinoma

Abstract The incidence of esophageal adenocarcinoma (EAC) has rising rapidly during the past four decades in the US and Western countries, becoming the dominant type of esophageal cancer and a significant clinical challenge. However, the prognosis of EAC patients is still poor with 5-year overall survival rate about 20%. There is an urgent need to identify novel therapeutic targets associated with EAC biology. NEK2 is a serine/threonine protein kinase of NEK (NIMA related kinase) family which has 11 members, NEK1-NEK11. NEK2 is frequently overexpressed in human cancers, associated with tumor progression and drug resistance. We detected the overexpression of NEK2 in both mRNA and protein levels in EAC cell lines and primary EAC tissues using qRT-PCR, western blotting, immunohistochemistry. Functionally, we demonstrated that overexpression of NEK2 in EAC cells promoted tumor cell growth. Targeting NEK2 using specific siRNAs and a recent NEK2 specific inhibitor NBI-961 in EAC cells significantly inhibited EAC tumor growth in vitro and in vivo in a xenograft mouse model. RNA-seq analyses indicate that NEK2 inhibition using NBI-961 impaired important signaling pathways such as EMT, IL6-JAK -STAT3, mTOR1 and DNA repair, and enhanced interferon alpha response pathway in EAC cells. Our data suggests that targeting frequently overexpressed NEK2 in EAC is a promising approach. Citation Format: Lei Chen, Heng Lu, Farah Ballout, Wael El-Rifai, Oliver Gene McDonald, Dunfa Peng. Targeting overexpressed NEK2 kinase in esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6968.