Two-Drug Combination,
Under Certain Circumstances, Can Eliminate Disease
New
research conducted by Harvard scientists is laying out a road map to one of the
holy grails of modern medicine: a cure for cancer.
As
described in a paper recently published in eLife, Martin
Nowak, a professor of mathematics and of biology and director of the Program
for Evolutionary Dynamics, and co-author Ivana Bozic, a postdoctoral fellow in
mathematics, show that, under certain conditions, using two drugs in a
"targeted therapy" -- a treatment approach designed to interrupt
cancer's ability to grow and spread -- could effectively cure nearly all
cancers.
"In
some sense this is like the mathematics that allows us to calculate how to send
a rocket to the moon, but it doesn't tell you how to build a rocket that goes
to the moon," Nowak said. "What we found is that if you have a single
point mutation in the genome that can give rise to resistance to both drugs at
the same time, the game is over. We need to have combinations such that there
is zero overlap between the drugs."
Importantly,
Nowak said, for the two-drug combination to work, both drugs must be given
together -- an idea that runs counter to the way many clinicians treat cancer
today.
"We
actually have to work against the status quo somewhat," he said. "But
we can show in our model that if you don't give the drugs simultaneously, it
guarantees treatment failure."
In
earlier studies, Nowak and colleagues showed the importance of using multiple
drugs. Though temporarily effective, single-drug targeted therapy will fail,
the researchers revealed, because the disease eventually develops resistance to
the treatment.
To
determine if a two-drug combination would work, Nowak and Bozic turned to an
expansive data set supplied by clinicians at New York's Memorial
Sloan-Kettering Cancer Center that showed how patients respond to single-drug
therapy. With data in hand, they were able to create computer models of how
multidrug treatments would work. Using that model, they then treated a series
of "virtual patients" to determine how the disease would react to the
multidrug therapy.
"For
a single-drug therapy, we know there are between 10 and 100 places in the
genome that, if mutated, can give rise to resistance," Nowak explained.
"So the first parameter we use when we make our calculations is that the
first drug can be defeated by those possible mutations. The second drug can
also be defeated by 10 to 100 mutations.
"If
any of those mutations are the same, then it's a disaster," he continued.
"If there's even a single mutation that can defeat both drugs, that is usually
good enough for the cancer -- it will become resistant, and treatment will
fail. What this means is we have to develop drugs such that the cancer needs to
make two independent steps -- if we can do that, we have a good chance to
contain it."
How good a chance?
"You
would expect to cure most patients with a two-drug combination," Bozic
said. "In patients with a particularly large disease burden you might want
to use a three-drug combination, but you would cure most with two drugs."
The
trick now, Nowak and Bozic said, is to develop those drugs.
To
avoid developing drugs that are not vulnerable to the same mutation, Bozic
said, pharmaceutical companies have explored a number of strategies, including
using different drugs to target different pathways in cancer's development.
"There
are pharmaceutical companies here in Cambridge that are working to develop
these drugs," Nowak said. "There may soon be as many as 100
therapies, which means there will be as many as 10,000 possible combinations,
so we should have a good repertoire to choose from.
"I
think we can be confident that, within 50 years, many cancer deaths will be
prevented," Nowak added. "One hundred years ago, many people died
from bacterial infections, and now they would be cured. Today, many people die
from cancer, and we can't help them, but I think once we have these targeted
therapies, we will be able to help many people -- maybe not everyone -- but
many people."
Story Source:
The
above story is reprinted from materials provided byHarvard University. The original article was written by
Peter Reuell.
Note: Materials may be edited for content and length. For further
information, please contact the source cited above.
Journal Reference:
1.
Ivana Bozic, Johannes G
Reiter, Benjamin Allen, Tibor Antal, Krishnendu Chatterjee, Preya Shah, Yo Sup
Moon, Amin Yaqubie, Nicole Kelly, Dung T Le, Evan J Lipson, Paul B Chapman,
Luis A Diaz, Bert Vogelstein, Martin A Nowak.Evolutionary dynamics of cancer
in response to targeted combination therapy. eLife, 2013 DOI:10.7554/eLife.00747.001
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Harvard University (2013, July 19). New plan of attack in cancer
fight: Two-drug combination, under certain circumstances, can eliminate
disease. ScienceDaily. Retrieved July 21, 2013, from
http://www.sciencedaily.com/releases/2013/07/130719112147.htm