By focusing on how cancer stem cells
metabolize, researchers may have uncovered a new way to defeat them: by
attacking their energy supply.
Tinkering with cell metabolism could
help to stop cancer stem cells.
Drug resistance is a sizable problem
for cancer treatment. Medications that might
initially work will soon become ineffective.
Scientists from the University of
Michigan Rowel Cancer Center in Ann Arbor are focusing on how cancer stem cells fit into this problem.
Cancer stem cells are a small subpopulation
of the cells in a tumor. Like standard stem
cells, they are able to give rise to a range of cell types.
They are thought to play a vital
role in cancer relapse and metastases because they are usually left untouched
by standard chemotherapy and radiation therapy.
As lead study author Dr. Max S.
Wicha claims, "When we use targeted therapies, they often only work for a
certain period of time, and then the cancer becomes resistant. A lot of that
resistance is from the cancer stem cells. They change form to evade the
targeted therapy."
Because of this shape-shifting
ability, Dr. Wicha concludes that "we're going to need multiple stem cell
therapies to attack multiple forms of stem cells."
Cancer cell metabolism
In his latest experiment, Dr. Wicha
analyzed how cancer stem cells metabolize, looking for chinks in their armor.
The results were recently published in the journal Cell
Metabolism.
Researchers previously demonstrated
that cancer stem cells are flexible and can switch between different states:
one wherein they remain dormant and another in which they grow rapidly. This
ability to switch helps cancer to thrive and spread.
Metabolism is particularly key when
the stem cell transitions from one state to another, making it a potential
target for cancer treatment. When the cells are in their dormant phase, they
require glucose, but when they become active and start dividing, they rely on
fuel provided by mitochondria, which are reliant on oxygen.
In order to disarm this metabolic
switch, Dr. Wicha and team used a two-pronged approach. Firstly, they used an arthritis drug, which
blocks mitochondria, and secondly, they manipulated glucose to block that
pathway.
"Rather than just try to use toxic chemicals to kill a
cell, we use the metabolism of the cell itself to kill the cancer."
Using this double-headed attack, the
scientists managed to knock out stem cells in a mouse model of breast cancer. Though this
work is in its early stages, and there are lot of outstanding questions around
cancer stem cells in general, these results are encouraging.
Because recent studies have found
links between metabolism and the immune system, the authors of this study see a
future where immunotherapies might be combined with a metabolic approach to
improve outcomes even further.
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