Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling

Previous studies have shown that cancer stem cells in tumors are responsible for the growth and spread of cancer. In a breakthrough study in 2003, Dr. Max s. Wicha and colleagues found that a small number of cells in cancer, cancer stem cells, are responsible for cancer growth and spread. Just kill stem cells to control cancer.

However, cancer is like a game of playing moles. After knocking it down in one place, it will bounce back in another place.

Now, researchers have found that cancer stem cells exist in more than one state and are very malleable, which means they can change shape and switch back and forth between dormant and fast-growing states. This plasticity determines two key characteristics of cancer: proliferation and spread.

Corresponding author Max S. Wicha said: "When we take targeted therapy, these therapies usually only work for a while, and then cancer develops resistance. Many of the resistance comes from cancer stem cells, which change forms to avoid targeted therapy. Therefore, we need a variety of stem cell therapies to attack various forms of stem cells."

Researchers quickly discovered that cellular metabolism controls this change in cancer stem cells, suggesting a possible way to attack stem cells.

Cells gain energy through oxygen-dependent mitochondria and sugar (or glucose). Cancer stem cells can take advantage of both pathways. In dormant state, it uses glucose; in the proliferative state, it relies on oxygen.

Therefore, the researchers attacked the metabolism in two ways. They used a drug that is currently used to treat arthritis, which works by blocking mitochondria; it also blocks metabolism by manipulating glucose. After testing in breast cancer mice, the researchers found that attack metabolism can defeat cancer stem cells.

"We are not trying to kill cells with toxic chemicals, but to use the metabolism of the cells themselves to kill cancer," Wicha explained.

In addition, the researchers also learned that the immune system is regulated by metabolism, suggesting the possibility of combining anti-stem cell therapy with immunotherapy. In the future, they hope  to  introduce this  concept into the clinic.