Infection with Kaposi's sarcoma virus (KSHV) can cause 3 types of tumor, including primary effusion lymphoma (PEL). Although KSHV has been known to cause tumors for many years, there are no effective therapies for the treatment of KSHV-induced tumors. Now, researchers from the University of Helsinki, Finland, have found that the small-molecule inhibitor Nutlin-3a has antitumor effects in a mouse xenograft model of PEL.
In the study, which appears online on March 15 in advance of publication in the April print issue of the Journal of Clinical Investigation, Päivi Ojala and colleagues show that Nutlin-3a induces human PEL cell lines to undergo cell death by a process known as apoptosis. Nutlin-3a was found to disrupt an interaction between the KSHV protein LANA and the human proteins p53 and MDM2, releasing p53 to mediate apoptosis. As treatment with Nutlin-3a induced substantial tumor regression in mice with established human PEL, reactivation of p53 using Nutlin-3a might provide a viable therapeutic for the treatment of individuals with PEL.
TITLE: Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas
AUTHOR CONTACT:
Päivi M. Ojala
University of Helsinki, Helsinki, Finland.
Phone: +358-9-191-25548; Fax: +358-9-191-25554; E-mail: Paivi.Ojala@helsinki.fi.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30945
Journal
Journal of Clinical Investigation