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Recurrent breast cancer (Photo credit: Wikipedia)

Reporter: Venkat Karra, Ph.D. 

There is no good treatmnet for triple-negative breast cancer cells. The standard of care is combination chemotherapy, and although it has a good initial response rate, a significant number of patients develop recurrent cancer,” says Yaffe, who is a member of the David H. Koch Institute for Integrative Cancer Research at MIT.

Yaffe and postdoc Michael Lee, lead author of the Cell paper, focused their study on a type of breast cancer cells known as triple negative, meaning that they don’t have overactive estrogen, progesterone or HER2 receptors. Triple-negative tumors, which account for about 16 percent of breast cancer cases, are much more aggressive than other types and tend to strike younger women.

In the new paper, published in Cell on May 11, the researchers showed that staggering the doses of two specific drugs dramatically boosts their ability to kill a particularly malignant type of breast cancer cells.

Of all combinations they tried, they saw the best results with pretreatment using erlotinib followed by doxorubicin, a common chemotherapy agent. The researchers found that giving erlotinib between four and 48 hours before doxorubicin dramatically increased cancer-cell death. Staggered doses killed up to 50 percent of triple-negative cells, while simultaneous administration killed about 20 percent. About 2,000 genes were affected by pretreatment with erlotinib, the researchers found, resulting in the shutdown of pathways involved in uncontrolled growth.

Here the catch is the ‘order’ and ‘time’ because if the drugs were given in the reverse order, doxorubicin became less effective than if given alone.

They also saw good results with erlotinib and doxorubicin in some types of lung cancer.

“The drugs are going to be different for each cancer case, but the concept that time-staggered inhibition will be a strong determinant of efficacy has been universally true. It’s just a matter of finding the right combinations,” Lee says.

The findings also highlight the importance of systems biology in studying cancer, Yaffe says. “Our findings illustrate how systems engineering approaches to cell signaling can have large potential impact on disease treatment,” he says.

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