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Scientists Seek to Establish Model of Prostate Cancer Dormancy

Scientists Seek to Establish Model of Prostate Cancer Dormancy

JERUSALEM--Tumor cells that are not eradicated by chemotherapy
or radiotherapy can enter a prolonged dormant state and thus pose
a continuous threat of tumor relapse in patients who are seemingly
"cured," Eitan Yefenof, PhD, said in an interview with
Oncology News International.

Although there is evidence that prostate cancer cells can enter
a prolonged quiescent period following therapy, little is known
about the mechanism underlying the induction and maintenance of
this dormant state.

Dr. Yefenof, of the Lautenberg Center for General and Tumor Immunology,
Jerusalem, and his colleagues at the University of Texas Southwestern
Medical Center, Dallas, led by Dr. Jonathan Uhr, have taken the
first step toward understanding the dormant state in prostate
cancer with their project to establish an experimental model of
human prostate cancer dormancy in nude mice.

"Very little is known about the biology of dormant tumor
cells and the cellular and molecular mechanisms that lead to the
dormant state," Dr. Yefenof said. "We are studying them
to see what kinds of genetic mutations are causing the dormant
state and how the dormant state can be terminated, eradicated,
or kept silent for an extended period so as not to evoke clinical
manifestations in the host."

Much of what is known about dormant tumor cells comes from work
done by Dr. Yefenof when he was a visiting professor at UT Southwestern
in 1993. "We developed an experimental model for tumor dormancy
using lymphoma cells. We think what we learned about the dormant
state from this model can be applied to carcinomas as well."

Dr. Yefenof believes that dormant tumor cells still have a malignant
genotype, but receive a growth inhibitor signal from the environment
that prevents their proliferation. The dormant cells may suddenly
become active if the inhibitory signal is somehow "turned
off" or if the cell itself develops "resistance"
to the signal.

"If the countermanding signal is removed, the cells will
regrow and produce a tumor," Dr. Yefenof said. Alternatively,
the dormant cells may acquire an additional mutation that renders
them insensitive or resistant to the external signal that had
been keeping them under check.


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