The Culprit is Cancer
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1982, Slamon submitted to NIH a grant proposal for funding to build
a human tumor bank using discarded tissue from breast, prostate,
colon and lung cancers and then screen the tissue for specific genetic
alterations. "The application essentially came back with a laugh
track," he recalls. Undeterred, Slamon and his team secured support
from the Jonsson Cancer Center Foundation and UCLA and forged ahead
with the human tumor bank plan.
the meantime, academic and commercial labs across the country were
isolating new genes. In 1986, a scientist at MIT discovered an important
gene involved in regulating cell growth. It was HER-2/neu - Human
Epidermal Growth Receptor No. 2.
was by now convinced of the logic of his approach, but many of his
peers remained dubious. " 'Oh, this lab is on a fishing expedition,'
" Slamon recalls his critics saying. "Well, we were fishing for
alterations that we might identify. But we felt that once we identified
one, we had the capacity to do the harder work of pulling out the
gene and introducing it into breast cancer cells to see if it really
had an association with a bad outcome. That was the most exciting
science of all. As soon as we had valid models, we could start testing."
breast cancer tissue, Slamon and his team began extracting DNA and
asking questions: Was the HER-2/neu gene changed? Was its structure
somehow rearranged? Was its expression present in some altered way?
it was. Instead of the single copy of HER-2 normally present in
a cell, Slamon found multiple copies in approximately 30 percent
of breast cancer samples. "This gene makes something called a growth
factor receptor," he explains. "It's a protein that sits like an
antenna on the membrane of the cell and receives signals from the
outside telling the cell to grow."
then looked at women who had the genetic alteration to see if tumors
they developed were in any way unusual compared to tumors of women
without HER-2. Sure enough, women with the alteration had far more
aggressive disease: They failed standard therapy, their disease
metastasized more quickly, they died sooner.
was hopeful, but he hadn't yet proved that HER-2 was causing the
cancerous cells to multiply out of control. The alteration might
only be a marker, what scientists call an epiphenomenon, that develops
along with the real culprit driving the cancer.