Genetic tracking identifies cancer stem cells in
patients
The gene
mutations driving cancer have been tracked for the first time in patients back
to a distinct set of cells at the root of cancer – cancer stem cells.
The international
research team, led by scientists at the University
of Oxford and the Karolinska
Institutet in Sweden
The researchers
say their findings, reported in the journal Cancer Cell, offer
conclusive evidence for the existence of cancer stem cells.
The concept of
cancer stem cells has been a compelling but controversial idea for many years.
It suggests that at the root of any cancer there is a small subset of cancer
cells that are solely responsible for driving the growth and evolution of a
patient's cancer. These cancer stem cells replenish themselves and produce the
other types of cancer cells, as normal stem cells produce other normal tissues.
The concept is
important, because it suggests that only by developing treatments that get rid
of the cancer stem cells will you be able to eradicate the cancer. Likewise, if
you could selectively eliminate these cancer stem cells, the other remaining
cancer cells would not be able to sustain the cancer.
'It's like
having dandelions in your lawn. You can pull out as many as you want, but if
you don't get the roots they’ll come back,' explains first author Dr Petter
Woll of the MRC Weatherall Institute for Molecular Medicine at the University
of Oxford.
The researchers,
led by Professor Sten Eirik W Jacobsen at the MRC Molecular Haematology Unit
and the Weatherall Institute for Molecular Medicine at the University of Oxford
Using genetic
tools to establish in which cells cancer-driving mutations originated and then
propagated into other cancer cells, they demonstrated that a distinct and rare
subset of MDS cells showed all the hallmarks of cancer stem cells, and that no
other malignant MDS cells were able to propagate the tumour.
The MDS stem
cells were rare, sat at the top of a hierarchy of MDS cells, could sustain
themselves, replenish the other MDS cells, and were the origin of all stable
DNA changes and mutations that drove the progression of the disease.
'This is
conclusive evidence for the existence of cancer stem cells in myelodysplastic
syndromes,' says Dr Woll. 'We have identified a subset of cancer cells, shown
that these rare cells are invariably the cells in which the cancer originates,
and also are the only cancer-propagating cells in the patients. It is a vitally
important step because it suggests that if you want to cure patients, you would
need to target and remove these cells at the root of the cancer – but that
would be sufficient, that would do it.'
The existence of
cancer stem cells has already been reported in a number of human cancers,
explains Professor Jacobsen, but previous findings have remained controversial
since the lab tests used to establish the identity of cancer stem cells have
been shown to be unreliable and, in any case, do not reflect the "real
situation" in an intact tumour in a patient.
'In our studies
we avoided the problem of unreliable lab tests by tracking the origin and
development of cancer-driving mutations in MDS patients,' says Professor
Jacobsen, who also holds a guest professorship at the Karolinska Institutet.
Dr Woll adds:
'We can’t offer patients today new treatments with this knowledge. What it does
is give us a target for development of more efficient and cancer stem cell
specific therapies to eliminate the cancer.
'We need to
understand more about what makes these cancer stem cells unique, what makes
them different to all the other cancer cells. If we can find biological
pathways that are specifically dysregulated in cancer stem cells, we might be
able to target them with new drugs.'
Dr Woll
cautions: 'It is important to emphasize that our studies only investigated
cancer stem cells in MDS, and that the identity, number and function of stem
cells in other cancers are likely to differ from that of MDS.'
The study was
funded by the Leukemia and Lymphoma Society, Leukaemia and Lymphoma Research,
the Knut and Alice Wallenberg Foundation and the National Institute for Health
Research (NIHR) Oxford Biomedical Research Centre (BRC).
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