The Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including primary effusion lymphoma (PEL), a subtype of highly aggressive non-Hodgkin lymphoma (NHL). PEL preferentially arises in immunocompromised patients, e.g., AIDS patients, but lacks of effective therapeutic options. Ceramide serves as a central mediator in sphingolipid metabolism and is referred to as a “tumor suppressor lipid”; however, its functional role in PEL survival and therapeutic value remain largely unknown. Our previous work demonstrated that targeting sphingolipid metabolism by either sphingosine kinase 2 (SphK2) inhibitor or exogenous ceramides induced significant PEL apoptosis and suppressed tumor progression. Recently, we have synthesized a series of new ceramide analogs with better stability and solubility. Our first screening indicated that at least 2 new compounds effectively inhibited PEL cell growth, through the complex mechanisms including induction of tumor cell apoptosis, cell cycle arrest, intracellular ceramide production, and viral lytic gene expression. By using an immunodeficiency mice xenograft model, we found that these selective ceramide analogs significantly repressed PEL progression in vivo. Ongoing work includes the identification of global gene profile affected by these new compounds within PEL cells using the NGS technology. We hope these new ceramide analogs can be developed as promising therapeutic strategies for prolonging the survival time of PEL patients and/or improving their life quality.

Citation Format: Lu Dai, Maryam Foroozesh, Zhiqiang Qin. Developing new ceramide analogs against AIDS-related lymphoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B019.