“That’s a big difference if they want to
see their kid graduate or another baby
being born,” Pao says.
A case of cancer
“Magical” drugs like these are still wishful thinking for most patients, though,
says John Iafrate, a molecular pathologist at Mass General and a pioneer of the
hospital’s tumor snapshot program. The
search for anticancer medications that
pinpoint specific genetic defects reminds
him of the early days of antiretroviral
therapy for HIV. Attacking
one tumor process may not
be enough to completely
eliminate the cancer, he
says, just as the antiretroviral drug AZT wasn’t able
to control HIV infections
on its own.
To leap forward, scientists have to find out
what makes each person’s cancer tick, so they
can go after it with the
right drug combination.
Iafrate and others are
testing a few dozen genes
known to be important in
many different cancers.
But that approach offers
limited information — and
in some cases can even
mislead doctors.
That’s what happened
in the case of a 78-year-
old man with a very rare
tumor on his tongue. Doctors treating the British
Columbia man had his
tumor tested for a small
number of mutations,
finding that the tumor
cells made twice as much
EGFR protein as normal cells do. A drug
prescribed to combat the change proved
futile; the cancer spread to the man’s
lungs.
At that point, the clinicians decided
they needed help. They turned to Steven
Jones and his team at Canada’s Michael
Smith Genome Sciences Centre at the
British Columbia Cancer Agency in
Vancouver. Jones’ team deciphered the
complete genetic blueprint of one of the
lung tumors. In a study published last
year in Genome Biology, the researchers
described the genetic mess: 7,629 genes
were duplicated, triplicated or more; at
least four chromosomes were missing
huge chunks of DNA; and four genes con-
tained mutations that would alter protein
products. Also, 1,078 genes had higher-
than-normal activity, while 1,986 others
were less active than normal.
Before treatment
After treatment
A drug targeting a
common mutation
in patients with spread-
ing melanoma reduced
tumor presence (dark-
ness in chest and abdo-
men) within 15 days.
Researchers examined the genetic
blueprints of the treatment-resistant
cancer and found nine new mutations
that weren’t in the original tumor or
the man’s normal DNA. And other bits
of DNA continued to be added and lost
as well. Jones and colleagues speculate
that only a carefully concocted cocktail
of drugs could have stopped the cancer,
which ultimately led to the man’s death.
Too little, too late
The case highlights how having a
tumor’s complete genetic profile — what
scientists call a genome sequence — can
change patient care. But the study is
also an exception. Most studies catalog
a tumor’s genetic changes long after it
has been removed from the body, when
it is far too late to influence treatment,
says Elaine Mardis, a genome scientist
at Washington University School of
Medicine in St. Louis.
Genome sequences aren’t often used
during early treatment because it can
take months to prepare samples, compile
the genetic blueprints and then analyze
the results. In a study published in the
April 20 Journal of the American Medical
Association, Mardis and her colleagues
showed that they could find the source of
a patient’s leukemia in just seven weeks,
a short enough time to affect treatment.
Still, Pao says clinical tests shouldn’t
take much longer than a week or two.
And besides costing valuable time, the
bill for a complete genetic blueprint can
be substantial. Some companies estimate that it costs $5,000 to $6,000 to
assemble a tumor’s whole genome.
Mark Boguski, a pathologist at
Harvard Medical School, thinks it’s a
bargain. “If I had cancer and $10,000,
I’d have two choices: Take a cruise
and check off my bucket list, or get my
genome sequenced,” he says. “I’d get my
genome sequenced, no question.”
But there are additional costs in
the bioinformatics. Cancer databases
that might help in interpreting genetic
details usually don’t present informa-
tion in clinically useful ways, Pao says.
Even for a doctor who has a patient’s
cancer genome in hand and knows all
