Breast cancer stem cells are believed to be the only source of tumor recurrence and are known to be resistant to radiation therapy and do not respond well to chemotherapy. Researchers now report for the first time that radiation treatment--in spite of killing half of all tumor cells during every treatment--converts other cancer cells into treatment-resistant breast cancer stem cells.

The generation of these breast cancer stem cells offsets the otherwise highly effective radiation treatment. If scientists can determine the processes and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, according to study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and UCLA department of radiation oncology at the University of California, Los Angeles’ (UCLA) Jonsson Comprehensive Cancer Center (USA). “We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine,” said Dr. Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA. “It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment.”

The study recently appeared February 10, 2012, in the early online edition of the journal Stem Cells. “Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects,” the study authors stated.
There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Dr. Pajonk and colleagues eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice. Using a unique imaging system Dr. Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment. The newly generated iBCSC were amazingly similar to breast cancer stem cells found in tumors that had not been irradiated, according to Dr. Pajonk.

The investigators also discovered that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated. Dr. Pajonk reported that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells. However, if confronted by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumor. “What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing,” Dr. Pajonk said. “The study may carry enormous potential to make radiation even better.”

Dr. Pajonk stressed that breast cancer patients should not be worried by the study findings and should continue to undergo radiation if recommended by their oncologists. “Radiation is an extremely powerful tool in the fight against breast cancer,” he concluded. “If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful.”
 

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