Harvard Professor Martin Nowak and Ivana Bozic, a postdoctoral fellow in mathematics, are the co-authors of a recent paper that caught my eye: Their research shows that using two so-called targeted therapy drugs, in certain circumstances, could eliminate the disease. This research does not itself offer the promise of cure, but is provocative. Here is how Nowak framed it: “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.”
The authors found 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, the drugs must be given together – a proposal that is not common today.
What they did: To determine if a 2-drug combination would work, Nowak and Bozic used an expansive data set supplied by New York’s Memorial Sloan Kettering Cancer Center that showed how patients respond to single drug treatmnt. With the data, they created computer models of how multi drug treatments would work. Using that model, they then treated a series of “virtual patients” to assess response to multidrug therapy.
Rationale: With a single-drug approach, there are 10 to 100 places in the genome that, if mutated, can give rise to resistance. So the first parameter that autors used was whether 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, it’s a disaster, with the cancer becoming resistant. So drugs must be developed such that the cancer needs to make 2 independent steps.
My take: Interesting thought experiment. THe proof is in the clinical trials that will be done going forward. I think of innumerable potential mutations in cancers, but all may be conveniently divided into roughly 12-13 paths. Whether targeting 2 or 10 spots in these pathways will be needed is unknown, but targeting therapy is already here, and will surely expand in the future. I’m Dr. Michael Hunter.
Harvard Gazette, 18 July 2013