When bortezomib is given to patients with Epstein-Barr virus?associated cancers, it may be able to activate viral replication and induce lysis of tumor cells, according to an article in the March 1 issue of Clinical Cancer Research.

In the current study, radiologists and oncologists from Johns Hopkins Medical Institutions visualized expression of a key Epstein-Barr virus gene, TK (thymidine kinase), with a gamma camera. Under baseline conditions, gene expression was very low or absent. However, when bortezomib was given to mice carrying virus-positive Burkitt’s lymphoma, gene expression was seen to markedly increase.

“The beauty of this is that you don’t have to introduce any reporter genes into the tumor because they are already there,” said senior author Martin G. Pomper, MD, PhD. “This is the only example we know of where it is possible to image activated endogenous gene expression without having to transfect cells.”

A variety of cancers are more likely to occur in people who have been infected with the virus, but not all patients with these cancers have such infections. The new technique may be applicable to patients whose tumors are positive for the virus.

When enough viral particles are produced, the tumor will burst, releasing the virus. In animal experiments, this experimental therapy, called lytic induction therapy, resulted in tumor death.

The direct imaging of viral gene expression was made possible because the key gene product, thymidine kinase, is closely related to a kinase expressed in herpes simplex virus and direct visualization had been achieved with an inject able radiolabeled compound, 2’-fluoro-2’-deoxy-beta-d-5-iodouracil-arabinofuranside (FIAU), and a gamma camera.

“To perform molecular-genetic imaging, we have always had to infect cells with active herpes simplex virus so that they can replicate, express TK, and only then could we use the FIAU tracer to make the cells light up,” Pomper says. “So we were hoping to find a way to turn latent Epstein-Barr virus on in these cancers, and use the thymidine kinase it then produces to enable us to see the virus-associated tumors with radiolabeled FIAU.”

Not only can FIAU light up the tumors, it can also potentially kill them, Pomper said. For imaging purposes, FIAU can carry a radionuclide that emits a low energy gamma photon, but it can also be engineered to carry therapeutic radionuclide, which is lethal to cells in which TK is activated.

Results of this study suggests that this strategy could be applied to other viruses associated with tumors, and that other drugs may potentially be used to activate these viruses, Pomper said: “Decade is only one of an array of new, as well as older agents, that can induce lytic infection, and a particular agent could be tailored for use in a specific patient through imaging.”