Circulating Breast Cancer Cells Can Switch HER2 Gene On-Off to Evade Treatment

Circulating Breast Cancer Cells Can Switch HER2 Gene On-Off to Evade Treatment

In women with metastatic breast cancer who have gone through several rounds of treatment, circulating tumor cells can switch on and off a gene called HER2, allowing them to better evade the effects of treatment.

The study, “HER2 expression identifies dynamic functional states within circulating breast cancer cells,” published in the journal Nature, paves the way for new treatment strategies for women with this type of advanced breast cancer.

Cancer cells continuously change in response to their environment. The flexibility by which they turn on or off genes contributes to the resistance to drug treatment many cancers develop, and studies of these genetic changes are crucial for the development of better treatments.

Researchers from the Massachusetts General Hospital Cancer Center were studying genetic changes in 13 women with advanced brain cancer when they stumbled on this surprising finding. All the women had breast tumors that expressed the ER (estrogen receptor) gene, but not the HER2 gene. The two genes are known to drive cancer progression of breast tumors.

To study genetic changes, researchers isolated circulating tumor cells found in the bloodstream. To their surprise, they found cells that had the HER2 gene switched on. In other cells, the gene remained off, just as it was in the main tumor.

After analyzing the cells further, the research team, led by Dr. Daniel Haber, discovered that the cells could convert from a state where the HER2 gene was switched on and then off again, all while the ER gene was constantly on.

The team discovered something even more crucial. The two types of cells depended on different stimuli to grow, and so were sensitive to different types of cancer drugs. Also, they switched in response to different types of environments. For example, oxidative stress or cytotoxic chemotherapy triggered the switch back to the cells with no HER2 expression.

Researchers figured that stopping both cell types from growing simultaneously was needed to prevent cells from converting to start a new tumor.

To test the theory, they treated the lab-grown cells as well as more advanced breast cancer models with the chemotherapy drug Taxol (paclitaxel) and a treatment more effective against the HER2 negative cells. This prevented tumor growth in the cancer models.

“Although more research is needed to uncover why HER2 has this dynamic on-and-off expression, these insights from our research are a positive development for a new treatment approach,” Haber said in a news release.