Multiple-Drug Combination therapies can eliminate cancer

Research conducted by Harvard scientists has revived hopes in modern medicine for a cure for cancer. Scientists recently developed a mathematical model which shows that a combination of two cancer drugs under certain conditions can treat and cure nearly all cancers. 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 metastasize -- could effectively cure nearly all cancers. This was in a paper recently published in eLife. The finding brings hope in the research and fight against cancers. Though the research is a simulation, Nowak said it does offer hope to researchers and patients alike. In the study, Nowak and Bozic turned to an extensive and robust data set obtained from 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 extrapolate and create computer models of how multidrug treatments would work. Using the created computer model, they then treated a number of "virtual patients" to determine how the disease would react to the multidrug therapy.

Nowak the lead scientist said "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. 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." According to Nowak, both drugs must be given simultaneously, for the two-drug combination to work -- an idea that runs counter to the way many clinicians treat cancer today. Both drugs could therefore have a potentiating effect or an interaction which boosts the overall effect on the cancer activity said one of the Medics.

"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" Said Nowak. The researchers have underscored the importance of multiple drug regimens saying that resistance to single drug use is uncommon.

"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."

However, cancer treating drugs like other chemicals are known to be highly toxic to the body yet such information may not necessarily be given from virtual patients. Therefore for more reliable results, real patients most probably guinea pigs will have to be used.