One of the most disheartening things about cancer care today is the amount of guesswork that goes into drug treatments. It isn't uncommon for patients to go through two, three or more therapies before finding success or running out of time.

Scientists now know that genetics explain why some drugs may work work miraculously in one person but not at all in another. Mike Hemann and Doug Lauffenburger of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology have just come up with evidence that timing may be just as critical.

The researchers reported in the journal Cell that their work shows that tumors evolve though various stages and that some are more vulnerable to drugs than others. This suggests, Hemann said in an interview, that there may be a "windows" of opportunity for drugs that had previously been written off as failures.

The team's work grew out of observations that the new arsenal of targeted therapy cancer drugs often appeared to have initial success, but that tumors came back within four to six months after having developed resistance. By using computational models and experiments on mice, they found that the progression of this resistance doesn't appear to be linear. That is, the patients aren't necessarily becoming more resistant to a drug over time. Instead it appears that the period of transition from a non-resistant state to a resistant state actually may be the time when it is most sensitive to drug therapy.

"You can think of it as replacing a roof on a house," Hemann explained. "The most sensitive time is when you've taken down the old roof but before you've put the new one back on."

Hemann said that if providers can predict the evolution of a tumor, they can target it along the way.

"If we know the route to resistance," he said, "we can ambush tumor cells."

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