Abstract 4614: Inhibition of NEK2 promotes chemosensitivity and reduces primary effusion lymphoma burden

Abstract

Abstract Non-Hodgkin lymphoma (NHL) is a common cancer in both men and women, and represents a significant cancer burden worldwide. Primary effusion lymphoma (PEL) is a subtype of NHL infected with Kaposi sarcoma-associated herpesvirus (KSHV). PEL is an aggressive and lethal cancer with no current standard of care, owing largely to its propensity to develop resistance to current chemotherapeutic regimens. Here, we report a reliance of PEL on the mitotic kinase, NEK2, for survival. Genetic and pharmacologic targeting of NEK2 resulted in caspase 3-mediated apoptotic cell death of PEL. Furthermore, inhibition of NEK2 significantly prolonged survival and reduced tumor burden in a PEL mouse model. We also report that the ABC transporter proteins, MDR1 and MRP, are most active in PEL and that NEK2 inhibition of PEL reduced the expression and activity of these ABC transporter proteins, which are known to mediate drug resistance in cancer. Additionally, NEK2 inhibition sensitized both viral and non-viral NHL to other chemotherapeutic agents such as rapamycin, resulting in enhanced cancer cell death. Overall, these data offer insight into the mechanisms underlying PEL survival and drug resistance, and suggest that NEK2 is a viable therapeutic target for PEL. Citation Format: Maria C. White, Jason P. Wong, Blossom Damania. Inhibition of NEK2 promotes chemosensitivity and reduces primary effusion lymphoma burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4614.