SCI transl Med: ten years! New anticancer drugs discovered by American scientists

March 11, 2019 / biourn / - researchers from the Westar Institute have created a drug to treat cancer associated with Epstein-Barr virus (EBV), which causes infectious mononucleosis In the study, published in Science Translational Medicine, the researchers described a class of inhibitors of EBV protein of Epstein Barr nuclear antigen 1 (EBNA1) Photo source: more than 90% of the world's adults will be infected with EBV, which can cause a lifetime latent infection of B cells, in some cases related to the occurrence of different types of tumors, such as Burkitt's lymphoma, nasopharyngeal carcinoma (NPC) and Hodgkin's lymphoma EBNA1 is a DNA binding protein, which is very important for virus replication and continuous proliferation in infected cells "EBNA1 is found in all EBV related tumors and does not look like any protein in the body." Professor Paul M Lieberman, co-author of the study and head of the research group on gene expression and regulation at the Westar Institute, said "These characteristics and the specific structure of the protein make it an attractive therapeutic target." Based on the 3D structure of the protein, Lieberman and his colleagues created a class of small molecular inhibitors that can inhibit its binding proteins, which were verified on NPC cells infected with EBV The researchers studied the therapeutic effects of these inhibitors on EBV related mouse tumor models, which were derived from transplanted tumor cells or patient derived tumor cells The researchers found that tumor growth slowed significantly in all mice, and the combination of radiotherapy or chemotherapy could further enhance the therapeutic effect "It took nearly a decade for this study to come up with clinical drug candidates from a concept." Troy E messick, Ph.D., lead author, co-author and senior scientist at Lieberman lab, said "We are very satisfied with the efficacy of these inhibitors in a series of preclinical studies, and we look forward to further in-depth study." EBNA1 inhibitors play an important role in the gene expression of EBV and host cells, which is related to the decrease of EBV DNA replication and the inhibition of EBV derived tumor promoting signals Importantly, the experimental results show that the treatment effect is significant, and there is no evidence of drug resistance after long-term use Reference: T.E Messick El al., "Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth," Science Translational Medicine (2019) Doi:10.1126/scitlandslide.aau5612