Combination of Chemotherapy Drugs Could Target Breast Cancer Stem Cells

Epigenetic changes can leave cancer stem cells vulnerable to a combination of 5-azacytidine and butyrate.

A combination of 5-azacytidine and the HDAC inhibitor butyrate were able to reduce breast cancer stem cells and improve survival rates in mouse models during a recent study.

"Most current chemotherapy does not kill the stem cells, which are the cells of origin, only the tumor mass," said study author Muthusamy Thangaraju, PhD.

Currently, these 2 drugs are used together to make tamixofen more effective. About 70% of breast cancer are positive receptors for estrogen and tamixofen blocks estrogen’s receptors, which reduces hormone levels. According to the study, published in Cancer Research, additional drugs reduce recurrence.

Researchers had evidence that these 2 additional drugs are able to effect at least 2 ways that allow stem cells to develop breast cancer, including the myoepithelial cells that allows the cancer to spread.

These drugs also help normalize altered gene expression and block growth-promoting signals, according to the study.

Specifically, the drug 5-azacytidine is an inhibitor of DNMT1, which is needed to maintain normal breast stem cells and healthy breast tissue. DNMT1 is more highly expressed in breast cancer compared with normal breast tissue.

When this gene is blocked, it eliminated 80% of breast tumors, even the most aggressive ones.

Signaling molecules such as RAD51AP1 and SPC25 are also overexpressed in breast cancer, enabling the growth and spread of cancer cells. The drug butyrate blocks excess levels of the molecules.

According to the study, stem cells make progenitor cells, which then produces breast tissue and cells. A change in gene expression can result in cancer stem cells making tumor and myoepithelial cells, which allows for metastasis.

Researchers concluded that these cancer-enabling epigenetic changes result in cancer stem cells that are susceptible to a combination of 5-azacytidine and butyrate.