Johns Hopkins scientists have discovered that women
treated for ovarian cancer are at increased risk of a rapid
and potentially fatal recurrence if their tumor cells have
high levels of a binding protein that triggers abnormal
growth and slows down cell death, both hallmarks of
malignancy.
"Now there's the possibility that testing for NAC-1
protein in cancer tissue removed during surgery might
identify women most at risk for recurrence and guide
doctors and patients to greater vigilance and extended
therapy," said Ie-Ming Shih, associate professor of
pathology at the
Johns
Hopkins Kimmel Cancer Center. The research also
suggests that drugs capable of blocking NAC-1 activity may
be a useful strategy in preventing and treating recurrences
as well.
A report on the research, the first to link NAC-1 to
cancer, appears in the Dec. 5 issue of the Proceedings
of the National Academy of Sciences.
"Because recurrent cancers are often what really kill
patients, and most ovarian cancer is diagnosed when it's
already advanced, our findings offer women a better chance
of catching or preventing recurrent disease early and
increasing survival," Shih said.
It is estimated that at least 60 percent of
advanced-stage ovarian cancer patients who appear to be
disease-free after initial treatment develop recurrent
disease, according to the researchers.
When the investigators compared levels of NAC-1 among
primary and recurrent tumor samples taken from 338 ovarian
cancer patients from two hospitals, they found that levels
of NAC-1 were significantly higher in recurrent tumors
compared with primary tumors taken from the same patient.
Women whose primary cancers had high levels of NAC-1 were
more likely to suffer a recurrence within one year.
Studying the functions of NAC-1, the researchers
genetically modified cells so they made both NAC-1 and a
component of the protein found at the ends of natural NAC-1
that is a binding site. In the modified cells, N130 capped
off NAC-1 proteins, disrupting their ability to bind with
each other. This action can prevent tumor formation and
kill cancer cells in experimental mice. Shih says that in
the future, drugs that mimic N130 can be used to treat
cancer.
This research was supported by the Department of
Defense and the National Institutes of Health.
Co-authors of the published research are Kentaro
Nakayama, Naomi Nakayama, Jim J.-C. Sheu, Antonio
Santillan, Ritu Salani, Natini Jinawath, Robert E. Bristow,
Robert J. Kurman and Tian-Li Wang, all from Johns Hopkins;
Ben Davidson, of the Norwegian Radium Hospital, Oslo,
Norway; and Patrice J. Morin, of the National Institute on
Aging, NIH.
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