Abstract 240: Therapeutic targeting of protein kinase ck2 in mycn-driven neuroblastoma

Abstract

Abstract Amplification of the MYCN oncogene occurs in about 30-40% of advanced neuroblastoma cases and is the most reliable predictor of poor prognosis. Protein kinase CK2 (casein kinase II) is a highly conserved serine/threonine kinase that can be effectively inhibited by small molecules. In fact, CX-4945, a potent, specific, ATP-competitive CK2 inhibitor, is currently tested in clinical trials to treat multiple cancers. However, the role of CK2 in MYCN-driven neuroblastoma remains unknown. To determine the relevance of CK2 in MYCN-driven neuroblastoma pathogenesis, we analyzed published microarray data and compared the expression of the CK2 subunits in primary neuroblastoma patients samples. We found that both CK2α and CK2α’ are upregulated in neuroblastoma patients samples with MYCN amplification, compared to the ones without MYCN amplification. To determine the effect of CK2 inhibition on neuroblastoma cells, we treated a panel of human neuroblastoma cell lines with the CK2 inhibitor CX-4945 and short hairpin RNA specifically targeting CK2α. CK2 inhibitor CX-4945 suppressed human neuroblastoma cell growth, mainly through inducing apoptosis, especially in the MYCN-amplified cells. More over, CK2α knockdown also induced cell apoptosis. In-vitro assay indicated that CK2 inhibition through either genetic or pharmacological approaches effectively reduced cell growth of human neuroblastoma cells primarily through induction of apoptosis. 14 days in-vivo treatment, CX-4945 significantly decreased tumor growth in mouse xenografts by subcutaneously implanting human KELLY neuroblastoma cells, but didn’t affect their body weight. These studies characterize the role of CK2 in neuroblastoma development, and provide valuable information about the relevance of CK2 as a target in MYCN-driven neuroblastoma. Note: This abstract was not presented at the meeting. Citation Format: Haiwei Lian, Ning Shen, Yun Zhou, Dun Li, Hui Feng. Therapeutic targeting of protein kinase ck2 in mycn-driven neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 240.