Triple-negative breast cancer is as bad as it sounds. The cells that form these tumors lack three proteins that would make the cancer respond to powerful, customized treatments. Instead, doctors are left with treating these patients with traditional chemotherapy drugs that only show long-term effectiveness in 20 percent of women with triple-negative breast cancer. Now, researchers at The Johns Hopkins University have discovered a way that breast cancer cells are able to resist the effects of chemotherapy -- and they have found a way to reverse that process. A report of their findings was published online in PNAS on December 1, 2014. Triple-negative breast cancers account for about 20 percent of all breast cancers in the United States, and 30 percent of all breast cancers in African-American women. In addition to being resistant to chemotherapy, these cancers are known to include a high number of breast cancer stem cells, which are responsible for relapses and for producing the metastatic tumors that lead to the death of patients with cancer. Previous research revealed that triple-negative breast cancer cells show a marked increase in the activity of many genes known to be controlled by the protein hypoxia-inducible factor (HIF). Given these past results, a research team directed by Gregg Semenza, M.D., Ph.D., of Johns Hopkins, decided to test whether HIF inhibitors could improve the effectiveness of chemotherapy. "Our study showed that chemotherapy turns on HIF and that HIF enhances the survival of breast cancer stem cells, which are the cancer cells that must be killed to prevent relapse and metastasis," says Dr. Semenza, the C. Michael Armstrong Professor of Medicine at Johns Hopkins and a Johns Hopkins Kimmel Cancer Center expert. "The good news is that we have drugs that block HIF from acting."
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