A mouse resistant to cancer,
even highly-aggressive types, has been created
by researchers at the University of
Kentucky. The breakthrough stems from a
discovery by UK College of Medicine professor of
radiation medicine Vivek Rangnekar and a team of
researchers who found a tumor-suppressor gene
called "Par-4" in the prostate.
The
researchers discovered that the Par-4 gene kills
cancer cells, but not normal cells. There
are very few molecules that specifically fight
against cancer cells, giving it a potentially
therapeutic application.
Funded by
several grants from the National Institutes of
Health, Rangnekar's study is unique in that mice
born with this gene are not developing tumors.
The mice grow normally and have no defects. In
fact, the mice possessing Par-4 actually live a
few months longer than the control animals,
indicating that they have no toxic side
effects.
"We originally discovered Par-4
in the prostate, but it's not limited to the
prostate. The gene is expressed in every cell
type that we've looked at and it induces the
death of a broad range of cancer cells,
including of course, cancer cells in the
prostate," said Rangnekar. "The interesting part
of this study is that this killer gene is
selective for killing cancer cells. It will not
kill normal cells and there are very, very few
selective molecules out there like
this."
To further investigate the
potential therapeutic benefits of this gene,
Rangnekar's team introduced it into the egg of a
mouse. That egg was then planted into a
surrogate mother.
"The mouse itself does
not express a large number of copies of this
gene, but the pups do and then their pups start
expressing the gene," Rangnekar said. "So,
we've been able to transfer this activity to
generations in the mouse."
The
implications for humans could be that through
bone marrow transplantation, the Par-4 molecule
could potentially be used to fight cancer cells
in patients without the toxic and damaging side
effects of chemotherapy and radiation
therapy.
"When a cancer patient goes to
the clinic, they undergo chemotherapy or
radiation and there are potential side effects
associated with these treatments," Rangnekar
said. "We got interested in looking for a
molecule which will kill cancer cells and not
kill normal cells, but also would not be toxic
with regard to the production of side effects to
the entire organism. We are thinking of
this in a holistic approach that not only would
get rid of the tumor, but also not harm the
organism as a whole. Before this animal
study, we published a lot of work indicating
that in cell culture, there's no killing of
normal cells. This is the proof that it doesnt
kill normal cells because the mouse is alive and
healthy."
Rangnekar admits there is much
more work to be done before this research can be
applied to humans, but agrees that is the most
logical next step.
"I look at this
research from the standpoint of how it can be
developed to the benefit of the cancer patient
and that's really what keeps us focused all this
time," said Rangnekar. "If you look at the pain
that cancer patients go through, not just from
the disease, but also from the treatment it's
excruciating. If you have someone in your
family, like I did, who has gone through that,
you know you can see that pain. If you can not
only treat the cancer, but also not harm the
patient, that's a major breakthrough. That's
happening with these animals and I think that's
wonderful."
The research was published in
the October edition of the journal Cancer
Research. Dr. Rangnekar holds the Alfred
Cohen, M.D., Endowed Chair in Oncology Research,
and serves as the associate director (for
translational research), at the Markey Cancer
Center.
