About new drugs for treating oligodendroglioma, the following article from Scientific American Mind, from 2010 had three different suggestions all involving stopping the cancerous stem cells from either multiplying out of control themselves, or causing other glial cells to do so.
New Hope for Battling Brain Cancer
Studies suggest that stem cells sustain deadly tumors
in the brain—and that aiming at these insidious culprits
could lead to a cure
By Gregory Foltz
Scientific American Mind, March/April 2010
Aiming at the Enemy
Nevertheless, the discovery of brain
tumor stem cells offers hope to victims of
brain cancer, because it suggests that
treatment strategies that specifically target
those cells could kill the cancer and
prevent it from recurring. One of the first
challenges is to find better ways to isolate
brain cancer stem cells. The molecular
flags on the cells—which include characteristic
DNA, RNA and proteins—found
as yet are not foolproof identifiers. Not
all glioma cells that sport CD133 are
brain cancer stem cells, and
not all brain cancer stem
cells carry this marker.
Thus, attempts to isolate
these cellular time bombs
may miss some of them.
Distinguishing brain
cancer stem cells from normal
stem cells is important
for designing therapies that
eradicate the former while
sparing the latter, which
are crucial for regeneration,
for repair and (in the
brain) maybe for learning.
For example, doctors might
employ monoclonal antibodies—
Y-shaped proteins that help to
destroy invading bacteria and viruses—
that target surface biomarkers unique to
brain cancer stem cells. Such molecular
tags might also reveal whether a brain
cancer is more or less aggressive and
which drugs are most likely to eradicate
it. After treatment, tests that look for the
presence of certain biomarkers in the
blood or spinal fluid may also make it
possible to detect a recurring tumor before
it has had time to grow.
. . . .
In 2009 neuro-oncologist Markus
Bredel, who directs the Brain Tumor Institute
Research Program at Northwestern
University, and his colleagues used a
systems biology approach to unearth a
network of genes that appears to play an
important role in malignant glioma. In
an analysis of gliomas from 501 patients,
they identified the most common genes
and genetic abnormalities among the
cancerous cells, along with their patterns
of expression. Many of the most active
genes, they discovered, are involved in a
complex system of interacting signaling
pathways that tells a cell when to grow
and when to stop. Certain patterns of
gene activity in these interacting networks,
they further learned, were associated
with better or worse patient survival.
They also identified what they called
“hub” genes that seemed to be key elements
in these networks, providing possible
targets for future medications. A
larger effort to dissect the molecular
anatomy of brain cancer is under way at
the Allen Institute for Brain Science in
Seattle, where researchers will be creating
a 3-D genetic map of these tumors
[see box on opposite page].
-------- BMP -------
Other researchers are finding drugs
that temper the toxicity of brain tumor
stem cells by coaxing them into a less
hazardous form. In a 2006 paper, for example,
cell biologist Angelo Vescovi of
the University of Milan-Bicocca in Italy
and his colleagues studied the effect that
a growth factor called bone morphogenetic
protein (BMP) had on glioblastoma
cells. In the normal brain, BMP directs
cells to differentiate, mature and
specialize. In their study, Viscovi’s team
showed that BMP had a similar effect on
human glioblastoma stem cells, causing
them to abandon their stem cell–like behavior
and become less aggressive. In
test tube experiments, BMP shrank the
number of stem cells within a tumor. It
also prevented the cancer cells from
growing into a tumor when they were
later implanted in a mouse brain. And
administering BMP after a glioblastoma
had been transplanted into the brain of
a mouse could block the growth of the
tumor and save the mouse’s life.
-------- Some anti-depressants and anti-psychotic drugs may interrupt signaling from cancerous glial stem cells ----------
Off-the-Shelf Treatments?
Intriguing new findings hint that
drugs used to treat certain common psy-
chiatric disorders may also be effective
against brain tumors—again, by targeting
brain tumor stem cells. In a study
published in 2009 Dirks and his colleagues
created cultures of glioma neural
stem cells on which they tested the efficacy
of various medications. In a trialand-
error screen of 450 approved drugs,
the researchers found that 23 drugs used
to treat mental illnesses such as depression,
anxiety and schizophrenia killed
the glioma stem cells.
These drugs all block or alter the
transmission or reception of neurotransmitters
(substances that pass information
between neurons), and that mechanism
probably underlies their toxicity to
brain tumors. During brain development,
normal neural stem cells need certain
chemical signals from their surroundings
to transform into mature nervous
system cells. Similarly, brain tumor
stem cells depend on chemical input to
survive and grow. Thus, such neuromodulatory
drugs may interfere with the
molecular messages that brain tumor
stem cells need to multiply and mature.
Testing of these neuromodulatory
drugs is still in the very early stages.
Currently a major effort is under way to
identify which of these compounds appear
most promising by screening them
against tumor cells in laboratory studies.
Once the most promising drugs are
identified, however, clinical trials should
start reasonably quickly because many
of these drugs have already been tested
for safety and approved by theFDAfor
other purposes.
Could an antidepressant treat brain
cancer? Dwayne Berg would certainly
like to know. Developing a new drug
typically takes decades, time that Berg
and other brain cancer patients do not
have. The promise of combating their
disease with available medications is
immediately appealing. Other new treatments
that target brain cancer stem cells,
too, remain unproved. Clinical trials for
many of them are just getting under way.
But for the first time in a long while, our
new understanding of brain cancer is
giving patients and doctors some degree
of hope