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A Novel Treatment for KSHV-infected Lymphomas

Kaposi’s sarcoma herpesvirus (KSHV) is a human tumor virus which causes Kaposi’s sarcoma and primary// effusion lymphoma (PEL).

PELs are aggressive lymphomas with reported median survival time less than six months after diagnosis.

Researchers at the University of Helsinki have discovered that activation of the p53 pathway offers a novel effective treatment modality for KSHV-infected lymphomas.

The findings by the research group of Dr. P?ivi Ojala (University of Helsinki) in collaboration with the groups of Professor Marikki Laiho (University of Helsinki), Dr. Pirjo Laakkonen (University of Helsinki), and Dr. Jürgen Haas (Max von Pettenkofer Institute, Munich & University of Edinburgh) open new options for exploiting reactivation of p53 as a novel and highly selective treatment modality for this virally-induced lymphoma.

The project involves scientists from two Academy of Finland National Centre of Excellence Programs, the Translational Genome-Scale Biology and Cancer Biology. The study will be published 15.3.2007 in the Journal of Clinical Investigation.

TP53 gene encodes a transcription factor (p53) that plays a central role in protecting cells from tumor development by inducing cell-cycle arrest or apoptosis via a complex signal transduction network referred to as the p53 pathway. TP53 gene is mutated or deleted in 50% of all malignant tumors.

A recently discovered strategy for p53 activation targets the interaction of p53 with its negative regulator MDM2. This is based on a potent and selective small-molecule inhibitor of the p53–MDM2 interaction, the Nutlin-3a, originally discovered by Dr Lyubomir T Vassilev (Roche Research Center, Nutley, NJ., USA). Nutlin-3a has been suggested to be a potential treatment option for cancers with wt p53.

PEL is a non-Hodgkin type lymphoma latently infected with KSHV, and it manifests as an effusion malignancy in Kaposi’s sarcoma patients. Ther
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