New technique may improve cancer treatment

CAMBRIDGE, Mass., March 20 (UPI) -- Scientists said Thursday that they have devised a way of predicting genetic mutations in cancer patients that confer resistance to anti-cancer drugs.

The screening method could lead to a new strategy for developing better and more specific cancer treatments, Dr. George Daley, a biologist at the Whitehead Institute at the Massachusetts Institute of Technology and principal investigator of the study, told United Press International.

The leukemia drug Gleevec targets a specific protein involved in a form of the cancer called chronic mylogenous leukemia. The gene that produces this protein continuously mutates and some mutations can confer resistance to the drug, meaning it no longer effectively inhibits the cancer in some patients.

Using the new screening technique, scientists can determine gene sites that are unable to mutate, which makes them possible targets for new cancer drugs, Daley said.

"It's a whole new strategy," he said. "It's a way of predicting the mutations patients are going to develop even before they are exposed to drugs," he said.

Carolyn Bruzdzinski, a geneticist and scientific program director with the American Cancer Society, said the finding is promising.

"It's all potential at this stage, but it's certainly a step in the right direction and could potentially accelerate the development of effective drugs," Bruzdzinski told UPI.

In the study, which appears in the March 21 issue of the journal Cell, Daley's team took leukemia cells and randomly caused mutations in the gene that produces the BCR/ABL protein, which Gleevec targets.

The cells then were exposed to Gleevec in a petri dish. Most cells died, but some survived. By sequencing the DNA of the cells that survived, the researchers were able to identify 15 mutations previously seen in patients resistant to Gleevec as well as 97 new mutations.

Daley said his team went further and identified regions of the gene that appeared to stay the same and not mutate. These areas may be unable to change because they may be critical to the function of the protein, Daley said.

Identifying these non-mutational areas could make it possible to design a drug that specifically targets those sites and thus avoid resistance, he said.

The technique could be applied to any cancer to determine mutations that might confer resistance to a drug, Daley said. This technique is "certainly not restricted to leukemia," he said.

It also could be used by physicians to determine when to switch a patient to another drug because they would be able to ascertain when the person had developed a mutation that was conferring resistance.

Pharmaceutical companies developing new cancer drugs are also interested in the screening technique, Daley said. Many target-specific drugs similar to Gleevec are in development and this screening method could be used to determine where mutations might occur and then develop companion compounds that could be used in conjunction with the original drug to help prevent resistance, he said.

Bruzdzinski agreed. "If you can predict (where mutations occur), you can then better inform the next line of drugs by developing a drug that will basically counteract the resistance," she said.

"It's what's been seen in HIV all over again," Daley said, referring to the strategy in which HIV/AIDS patients are given a combination of three or more drugs that act on different parts of HIV and thus lower the chance of the virus developing resistance.

"This study really suggests that's what's going to have to be done with cancer," he said.

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(Reported by Steve Mitchell, UPI Medical Correspondent, in Washington)