Inside Salk - October 2009 - page 9

Inside SalkOctober 2009
Other strategies being tested in the Cancer Center seem born out
of science fiction, but show great promise.
Clodagh O’Shea
, assistant
professor in theMolecular and Cell Biology Laboratory, and her team
have developed amodified adenovirus, normally associated with upper
respiratory infections in humans, to undergo selective lytic replication in
p53-deficient cancer cells while leaving all other tissues intact.
Once introduced into the tumors, the virusmultiplies and causes the
cancer cells to implode – releasing thousands of viral offspring in the
process to seek out more cancer cells. Initial clinical trials in theUnited
States using an early version of themodified virus showed encourag-
ing results when it was injected directly into the tumor. However, O’Shea
believes the latest modified virus will be highly effective.
“In an ideal world, it would be really amazing if we could inject it
systemically so it could spread throughout the body and find distant micro
metastases in places where we don’t even know the cancer has spread,”
O’Shea says.
“However, the virus we work with is not a naturally blood-bourne virus,
so there are factors that can limit its activity. That’s why we are also turn-
ing to different serotypes/subgroups of virus that naturally infect different
tissues, such as the colon and the kidney.”
In order to really understand cancer, however, Dulbecco suggested in
a 1986 Science article that the human genome would first need to be
sequenced so that it could be compared to its cancer counterpart. Four
years later the Human Genome Project was initiated by an international
group of scientists and completed in 2000.
“Now that it’s cheaper to sequence, it’s clear that cancer cells have
hundreds of mutations, whichmakes it more difficult to knowwhich genes
are important,”Hunter says. “But in the long run, what we hope is that
if enough cancer genomes are sequenced, commonalities will begin to
emerge for particular cancer types so that they can be correlated with
more effective treatments.”
Most of the cancer-therapy drugs available today work to counteract
the uncontrolled activity of oncogenes as a result of p53mutation. But
more is being done to find treatments for the other 50 percent of cancers
where p53 is not damaged. In such cases, there are two proteins that are
working in conjunction to degrade or completely inactivate the p53 gene:
Mdmx2 andMdmx.
Assistant Professor ClodaghO'Shea (right)
withUCSDgraduate student Kristen Espantman
…we are also turning to different
serotypes/subgroups of virus that naturally
infect different tissues, such as the colon
and the kidney.
– Clodagh O’shea
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