by Frank Pajonk, M.D., Ph.D.
Breast cancer stem cells
are thought to be the sole source of tumor recurrence and are known
to be resistant to radiation therapy and don’t respond well to
Now, researchers with the UCLA Department of Radiation Oncology at
UCLA’s Jonsson Comprehensive Cancer Center report for the first time
that radiation treatment - despite killing half of all tumor cells
during every treatment - transforms other cancer cells into
treatment-resistant breast cancer stem cells.
The generation of these breast cancer stem cells counteracts the
otherwise highly efficient radiation treatment.
If scientists can
uncover the mechanisms and prevent this transformation from
occurring, radiation treatment for breast cancer could become even
more effective, said study senior author Dr. Frank Pajonk, an
associate professor of radiation oncology and Jonsson Cancer Center
“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 Pajonk, who also is a scientist
with the Eli and Edythe Broad Center of Regenerative Medicine at
“It was remarkable
that these breast cancers used the same reprogramming pathways
to fight back against the radiation treatment.”
The study appears Feb.
13, 2012 in the early online edition of the peer-reviewed journal
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 states.
There are very few
breast cancer stem cells in a larger pool of breast cancer cells.
In this study, Pajonk
and his team 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 that 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
The newly generated
iBCSC were remarkably similar to breast cancer stem cells found in
tumors that had not been irradiated, Pajonk said.
The team also found 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.
Pajonk said 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 challenged
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,”
“The study may carry
enormous potential to make radiation even better.”
Pajonk stressed that
breast cancer patients should not be alarmed by the study findings
and should continue to undergo radiation if recommended by their
“Radiation is an
extremely powerful tool in the fight against breast cancer,” he
said. “If we can uncover the mechanism driving this
transformation, we may be able to stop it and make the therapy
even more powerful.”
This study was funded
Breast Cancer Research Program
Comprehensive Cancer Center has more than 240 researchers and
clinicians engaged in disease research, prevention, detection,
control, treatment and education.
One of the nation's
largest comprehensive cancer centers, the Jonsson center is
dedicated to promoting research and translating basic science into
leading-edge clinical studies.
In July 2011, the
Jonsson Cancer Center was named among the top 10 cancer centers
nationwide by U.S. News & World Report, a ranking it has held for 11
of the last 12 years.