Viral
warfare on cancer has been a dream of researchers for
many years. The theory is that if a virus rigged
with so-called "reporter genes" could be introduced
inside the tumour cells it would destroy them from within.
Now a team at Johns Hopkins has
found a way to use Epstein-Barr viruses (EBV) already
asleep inside tumour cells to selectively target treatment.
A variety of cancers, including four types of lymphoma,
nasopharyngeal and gastric cancers are more common in
individuals who have latent EBV infections.
"The beauty of this is that you
don't have to introduce any reporter genes into the
tumour because they are already there," said radiologist
and study author Dr Martin G Pomper in a statement issued
by the American Association for Cancer Research.
The team found that either of two
commercially available products including the
multiple myeloma drug bortezomib could be used
to 'awaken' the dormant virus and push it into the lytic,
or reproductive, phase of its life cycle. Once that
happens, the tumour cell will start to express viral
thymidine kinase (TK), an important enzyme for EBV reproduction.
But the protein can also be used to visualize the EBV-containing
tumour cells the radiolabelled chemical fialuridine
(FIAU) will attach to TK, causing the cells to light
up on a gamma camera.
The team tested the theory in mice
with Burkitt's lymphoma, the cancer most often associated
with EBV. "[Bortezomib] woke up the virus in the tumours,
which increased viral load by 12-fold, all the while
cranking out TK," Dr Pomper explained. "An injection
of FIAU made it easy to image the tumours with virus
in them."
The idea, of course, is not just
to visualize the tumour cells but to destroy them. While
in this instance, radio-labelled FIAU was used to image
the tumour cells, the compound can be engineered to
contain "therapeutic radionuclides" which would selectively
destroy cells in which TK is expressed.
The technique is described in the
March 1 issue of Clinical Cancer Research.
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