A new combination of drug therapies may prove effective in treating triple-negative breast cancer in human patients, according to a recent study published by researchers at Harvard Medical School and Baylor College of Medicine.
Triple-negative breast cancer is one of three classes of breast cancers and the only one that currently has no readily accessible treatment, said HMS Professor Stephen J. Elledge, the principle investigator for the Harvard lab.
The only treatment option for patients with these tumors is chemotherapy, and the median survival rate for such patients is very low.
The research sought to identify classes of molecules that, when down regulated, cause a cell to gain cancerous properties.
The study, which was published last month in the journal Cell, reported that the absence of a tyrosine phosphatase enzyme called PTPN12 caused human mammary cells to gain cancer-like properties in vitro.
The researchers separately found that PTPN12 was inactive in more than 50 percent of the triple-negative breast cancers tested, showing that the enzyme plays a significant role in this class of breast cancer, Elledge said.
Thomas F. Westbrook, a former postdoctoral fellow in Elledge’s Harvard lab and currently leading the research group at Baylor, discovered the PTPN12 enzyme while still at Harvard.
That enzyme is known to deactivate another group of enzymes called receptor tyrosine kinases that are responsible for cell growth.
So when PTPN12 is inactivated, cells are free to grow and divide rapidly, like cancer cells.
The research group identified three tyrosine kinases that are specifically regulated by PTPN12. These results indicated that the misregulation of these three enzymes could be a leading cause of triple-negative breast cancer, according to the study.
“If we figure out how to inhibit different kinases together, we might be able to treat this disease,” said Elledge.
The researchers tested in mice a combination of two FDA-approved, on-the-market drugs that are already used to treat other cancers and that inhibit the desired kinases. One drug, Tykerb, is known to inhibit two of the enzymes, and another, Sutent, is known to inhibit the third.
The study found that tumors in mice that were treated with a combination of both drugs shrank by more than 90 percent, and life expectancy for these mice more than doubled.
The researchers are now in the process of negotiating with drug companies to design a Phase II clinical trial that will test the new therapy in humans.
Ellidge said, “It may take two to three years to set up a clinical trial and get results, and then we can determine whether there will be a therapy.”
Ellidge said that while the research group has identified some of the kinases that are activated in triple-negative breast cancer, there is still more research to be done in order to understand the disease mechanisms completely.