Breast cancer recurrence is a complicated and multifaceted process with multiple underlying causes. While chemotherapy is a popular treatment for breast cancer, it is crucial to highlight that chemotherapy does not cause recurrence. Chemotherapy, on the other hand, is used to target and kill cancer cells in the body.
According to a recent study published in the open-access journal PLOS Biology by Ramya Ganesan of Emory University, US, and colleagues, a common chemotherapy treatment injures surrounding non-cancer cells, which can then awaken dormant cancer cells and encourage cancer growth. The discovery is significant for understanding cancer recurrence and may point to key new prevention targets.
Cancer treatment advances, such as chemotherapy, have substantially lowered mortality rates for many types of cancer, including breast cancer. Despite this, up to 23% of breast cancer patients will have a recurrence during the first five years. Treatment is intended to destroy all cancer cells, however, certain cells frequently enter a dormant condition, in which they cease dividing and become insensitive to chemotherapeutic medicines. When dormant cells reawaken and begin dividing again, recurrence occurs.
Our paper highlights a deleterious effect of cancer chemotherapy: release of stromal IL-6 and G-CSF by taxane chemotherapy awakened dormant breast cancer cells, a postulated mechanism for tumor relapse. Transient inhibition of cytokine signaling during chemotherapy treatment may prevent tumor recurrence.
Dr. Ganesan and Dr. Sukhathe
Some research have suggested that chemotherapy may enhance dormancy escape, however, the mechanism of this action is unknown. The scientists investigated this subject using both a cell model and a mouse model of breast cancer.
The cell model included both cancer cells and non-cancer stromal cells, which are connective tissue cells prevalent in breast and other tissues. They used the chemotherapeutic medication docetaxel at physiologically relevant concentrations and discovered that even at extremely low dosages, stromal cells were harmed but cancer cells were not, and that treatment caused cancer cells to enter the cell cycle again.
Chemotherapy medications, on the other hand, can have side effects and long-term repercussions on the body, including damage to healthy cells and tissues. This damage can sometimes cause difficulties or alterations in the tissue environment, which can contribute to the return of breast cancer in rare situations.
The driver of this reawakening of dormant cells, the authors showed, was release of two key cell signaling molecules, granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) by the injured stromal cells, which acted on the dormant cells to promote their growth, both in vitro and in vivo. That provided the team with potential anti-cancer targets, and they showed that antibodies that neutralized either G-CSF or IL-6, or a drug that blocked the mediator of those signals within cancer cells, inhibited awakening from dormancy due to docetaxel treatment.
These discoveries have several significant consequences. First, they emphasize the relevance of surrounding cells, rather than only cancer cells, in determining treatment response. Second, they give a putative molecular basis for the discovery that high blood IL-6 levels are related with early recurrence in breast cancer patients following chemotherapy, thus improving the utility of that biomarker in treatment planning. Third, they present new targets for averting recurrence.
“Our paper highlights a deleterious effect of cancer chemotherapy: release of stromal IL-6 and G-CSF by taxane chemotherapy awakened dormant breast cancer cells, a postulated mechanism for tumor relapse,” Dr. Ganesan and Dr. Sukhathe add. Transient inhibition of cytokine signaling during chemotherapy treatment may prevent tumor recurrence.”
