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Study Suggests How Some Cancers Resist Treatment
Date:4/1/2010

ykerb), used to treat breast cancer. Most of the drugs were provided for free by their manufacturers.

"We always found a small population of cells resistant to treatment and arising at significantly high frequency, [so] we thought it can't be genetic. The numbers just didn't make sense," Settleman said.

But the cells, once removed from the "drugged" environment, gave rise to a new generation of cells that were again susceptible to the drug therapies.

"Cells could randomly acquire and relinquish that drug-tolerance quality at low frequency so that any cell could potentially become drug-tolerant for a period of time, then surrender that ability," Settleman explained. This may be a way for the cells to survive as a group, with individual cells "compromising something for the good of the population," he stated.

An enzyme that changes chromatin, part of the structure of chromosomes, is necessary for a cell to develop tolerance. Although there are no drugs that can inhibit this enzyme, compounds that blocked a group of related enzymes did manage to kill off the drug-resistant cells, the researchers said.

"We discovered that there are inhibitors of certain chromatin-modifying enzymes that can actually selectively kill drug-tolerant cells," Settleman said. "That's where the therapeutic opportunity comes in. We showed that when you combine one of the chromatin-modifying enzyme inhibitors with [a drug] that treats most of the cells, you can wipe out most of the population."

The researchers are now starting a trial to combine an enzyme inhibitor with a lung cancer drug to see if they can prevent the development of resistance.

More information

Learn more about cancer drug resistance at Emory University.



SOURCES: Jeffrey Settleman, Ph.D., scientific director, Massachusetts General
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