Pathway That Influences Growth of Breast Cancer Stem Cells Revealed

A pathway linked to a gene called PTEN is important for the growth of breast cancer stem cells, according to scientists at the University of Michigan Comprehensive Cancer Center.

In the same study, the researchers have also found that a drug that interferes with that pathway can lead to an up to 90 percent decrease in the number of cancer stem cells within a tumour.

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Reporting their finding sin the journal PLoS Biology, the researchers pointed out that PTEN is the most frequently inactivated tumour suppressor gene in several cancers, including breast cancer, where it is inactivated in about 40 percent of patients.

The researchers also highlighted the fact that PTEN is linked to poor outcomes and is associated with aggressive cancers resistant to chemotherapy and current targeted therapies.

During the study, they deleted PTEN in tumours grown in cell cultures and in mice, and found an increase in the number of stem cells.

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Looking at pathways associated with PTEN, the researcher found that a pathway called PI3-K/Akt regulated the cancer stem cell population by activating another stem cell pathway, Wnt, which is also implicated in multiple cancer types.

"Although there has been considerable progress in identifying cancer stem cells in a variety of tumor types, the pathways that drive the transformation of these cells are not well understood," says lead study author Dr. Hasan Korkaya, research investigator in internal medicine at the U-M Medical School.

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Breast cancer stem cells represent fewer than 5 percent of the cells in a tumour, but are believed to be responsible for fuelling a tumour's growth and spread. It is believed that the ultimate cure of cancer will require killing these cells.

In the current study, the researchers treated tumours in mice with a drug called perifosine, which inhibits the Akt pathway, or docetaxel, a standard chemotherapy drug.

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The docetaxel alone showed no effect on the number of cancer stem cells in the tumour. But adding perifosine reduced the cancer stem cell population by up to 90 percent.

The researchers also observed that the cells treated with perifosine, either with or without docetaxel, were less likely to grow a secondary tumour, compared to the cells treated with just docetaxel.

"This is most exciting since perifosine and other drugs that target this pathway are currently in clinical development. If cancer stem cells do contribute to tumor relapse, then adding drugs that target these cells may help to make our current therapies more effective," says study senior author Dr. Max S. Wicha, Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

Source-ANI
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