Mutations in the BRCA1 breast cancer gene appear to be linked
with the loss of a protein important for putting the brakes on cell
growth, a finding that could lead to new therapies, researchers
said on yesterday.
The breakthrough could lead to more effective therapies for
women with an aggressive and especially deadly cancer known as
triple-negative that does not respond to current advanced drugs,
the researchers said.
"It doesn't have a good target for therapy at this point," said
Dr Ramon Parsons of Columbia University Medical Center in New York,
who worked on the study.
Scientists have known for more than a decade that women with
certain alterations in the BRCA1 gene were at high risk for breast
cancer. What they have not understood is exactly how a mutation in
this gene leads to cancer.
Researchers at Columbia, working with a team at Sweden's Lund
University, now believe mutations in the BRCA1 gene can leave cells
incapable of repairing routine DNA damage. When such damage occurs
in a protein called PTEN, which regulates the growth of cells, cell
growth is unchecked and tumors form.
Women with faulty copies of BRCA1 or BRCA2 have a 50 to 85
percent chance of getting breast cancer. Mutations in these genes
account for 5 to 10 percent of breast cancer cases.
Most breast tumors are called estrogen-receptor positive,
because they are fuelled by the hormone estrogen. About 20 percent
are HER2-positive, because a protein called HER2 is involved.
A third type is driven by the hormone progesterone.
These types of cancer have good treatments.
Then there are basal-like or triple-negative tumors, so named
because they lack estrogen, progesterone or HER2 receptors needed
for most breast cancer drugs to work.
"The basic idea is that BRCA1 is a repair enzyme that is
involved in coordinating the repair of double strand DNA breaks,"
said Parsons said.
"When it is mutated, it is no longer present in a cell. If a cut
occurs in PTEN, there is no way for this cell to fix it," said
Parsons, whose study was published in Nature Genetics.
(Agencies via China Daily December 10, 2007)