Researchers from the Department of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center report that radiation treatment transforms cancer cells into treatment-resistant breast cancer stem cells, even as it kills half of all tumor cells.1
“When we look at early-stage cancer patients, we compare patients receiving exactly the same treatment, and some fail and some are cured, and we can't predict who those patients will be,” says Frank Pajonk, MD, PhD, the study's senior author and an associate professor of radiation oncology and Jonsson Cancer Center researcher.
In some cases, cancer stem cells are generated by the therapy, but scientists do not yet understand all the mechanisms that cause this to occur. If they can determine the pathway and remove the reprogramming of cancer cells, they ultimately may be able to reduce the amount of radiation given to patients along with its accompanying side effects, says Dr. Pajonk.
The investigators found that induced breast cancer stem cells (iBCSCs) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells in regenerative medicine.
In the study, Dr. Pajonk and colleagues eliminated the smaller pool of BCSCs and then irradiated the remaining breast cancer cells and put them in mice. They were able to observe the initial generation into iBCSCs in response to the radiation treatment through a unique imaging system. These new cells were highly similar to the BCSCs that had been found in tumors that had not been irradiated. They also found that these iBCSCs had a more than 30-fold increased ability to form tumors than the nonirradiated breast cancer cells.
Their findings show that if tumors are challenged by certain stressors that threaten them (such as radiation), they generate iBCSCs that may, along with surviving cancer stem cells, produce more tumors.
The researchers' work continues as they begin to identify the pathways and several classes of drugs to prevent this process from occurring. To date, they have identified 2 different targets and drugs that could prevent it. The group has published their results of the study in breast cancer but also has made similar observations in both glioblastoma and head and neck cancer.
Dr. Pajonk says the study does not discredit radiation therapy. “Patients come to me scared by the idea that radiation generates these cells, but it truly is the safest and most effective therapy there is.”