According to the head author of the study, Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology, "Over-expression of the EZH2 protein has been linked to breast cancer progression, but the molecular details of that connection were unknown…this research connects EZH2 to the growth of breast tumor-initiating cells." The chain of events that improves the self-renewal, survival, and growth of breast cancer stem cells can be started by the oxygen-starved portions of a tumor, which in turn stimulates a protein that causes an over-expression of EZH2.
In addition, the team also discovered that two separate drugs stop the chain of molecular events, thereby stopping the creation of breast tumor-initiating cells. The researchers tested five anti-cancer drugs against a culture of breast cancer cells in tumor samples of human breast cancer in a mouse model. One of the drugs, Sorafenib, a RAF inhibitor, eliminated more cancer stems cells and blocked tumor formation. Because Sorafenib inhibits multiple targets, so the researchers also tested a drug in the experimental stage called AZD6224, which specifically inhibits the MEK-ERK cascade launched by RAF1. The researchers discovered that this drug eliminated the EZH2-promoted breast cancer stem cells and blocked the formation of precancerous mammospheres.
According to Dr. Hung, "The drugs' inhibition of the breast tumor-initiating cells reveals a previously unidentified therapeutic effect for RAF1-ERK inhibitors to prevent breast cancer progression…AZD6244 is being tested in multiple clinical trials, and it will be interesting to see whether the cancer-stem-cell-killing ability will be induced in those trials.”
Source: University of Texas M. D. Anderson Cancer Center