Abstract 2099: Novel inhibitors of NFkB inducing kinase (NIK) are cytotoxic for myeloma cell lines with NIK-dependent activation of NFkB.

Abstract

Abstract NFkB activity is critical for survival and proliferation of normal lymphoid cells and many kinds of B-cell tumors, including multiple myeloma (MM). NFkB activating mutations, which are apparent progression events, enable MM tumors to become less dependent on bone marrow signals that activate NFkB. Mutations that activate NFkB-inducing kinase (NIK) protein are the most prevalent among the many kinds of NFkB mutations in MM tumors. NIK is the main activating kinase of the alternative NFkB pathway, although over-expression of NIK also can activate the classical pathway. Three Amgen compounds (two NIK inhibitors and an isomeric control) were tested with human myeloma cell lines. These specific NIK inhibitors are selectively cytotoxic for cells with NIK-dependent activation of NFkB. The combination of NIK-inhibitors with IKKβ-inhibitors or dexamethasone show a synergistic effect that might more efficiently target some MM tumors. Citation Format: Yulia N. Demchenko, Walter Michael Kuehl. Novel inhibitors of NFkB inducing kinase (NIK) are cytotoxic for myeloma cell lines with NIK-dependent activation of NFkB. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2099. doi:10.1158/1538-7445.AM2013-2099 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.