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Re: Non-Specialized cell
Last month there was a discussion about stem and
differentiated cells. The following appeared in
Monday's Washington Post. It highlights new findings
about cancers and why they are so hard to kill with
radiation or chemotherapy.
--- jjacobus@mail.nih.gov wrote:
How to Kill Cancer So It Doesn't Grow Back
By Rob Stein
In Greek mythology, a terrifying swamp monster known
as Hydra would regrow two heads for every one lost
when one of the serpent's many necks was severed,
making the beast nearly impossible to slay. Modern
scientists think they may have discovered why cancer
often behaves like Hydra, refusing to die despite
every seemingly mortal blow that medicine inflicts
upon it.
Current cancer therapies may attack only the
equivalent of Hydra's head -- the majority of cancer
cells removed by surgery or destroyed by radiation and
chemotherapy. Spared is a crucial pool of mutant
cells that acts as the source of the malignancy,
leaving the cancer able to rise again and again.
According to this theory, which has steadily been
gaining credence, the only effective strategy for
defeating cancer will be found in treatments that
stanch cancer's ability to regrow, such as what
Hercules did when he finally slew the beast of ancient
Greece by cauterizing each of the monster's necks.
In the case of cancer, the solution would lie in
stamping out the highly specialized cells, known as
cancer stem cells, that appear to give rise to the
cancer in the first place. Such cells are largely
impervious to current treatments, enabling them to
lurk silently until they repeatedly spawn new tumors,
either in the same part or in other parts of the body.
"What we've been doing is simply making the tumor
shrink -- leaving the equivalent of the source of the
head behind. So it just regrows," said Michael Clarke,
a professor of medicine at the University of Michigan
in Ann Arbor, who has found evidence for the existence
of breast cancer stem cells. "We need to figure out
how to sever the head so it doesn't grow back."
In addition to breast cancer, scientists have
produced evidence for the existence of cancer stem
cells in two leukemias and a variety of brain cancers.
In the most recent evidence, published in the Aug. 12
issue of the New England Journal of Medicine,
researchers at Stanford University showed that among
the millions of cancerous cells found in patients
suffering from chronic myelogenous leukemia, only a
small, discrete population had the ability to
replenish the cancer.
"We showed that only certain cells have the ability
to self-renew," said Irving Weissman, who directs
Stanford's Institute for Cancer/Stem Cell Biology and
Medicine.
These cells appear to have specific characteristics
-- they are mutant versions of normal stem cells,
which are the immature versions of all cells that have
been the focus of attention in recent years because of
their potential for treating a host of ailments.
It remains unclear how cancer stem cells originate.
But they probably arise as a result of genetic defects
or exposure to toxins, researchers said.
"Normal stem cells are regulated by the body to make
just the amount you need," Weissman said. "But a
cancer stem cell has broken out of that control. It
self-renews in an unregulated fashion. Its
self-renewal gets way too big."
Regardless of the cause, scientists are urgently
trying to identify cancer stem cells for every type of
malignancy.
"We're going to keep going through each and every
human cancer to isolate each of the cancer stem cells
and show what their properties are so one can look for
new kinds of therapies," Weissman said.
Identifying the properties of the cancer stem cells
could provide crucial information, according to Peter
Dirks, a neurosurgeon at the University of Toronto who
has found evidence for cancer stem cells in every form
of brain cancer he has examined.
Brain cancer tumors that tend to be more aggressive
appear to have higher concentrations of cancer stem
cells, he said. "We're trying to apply this to patient
prognosis," Dirks said. "This may identify which
tumors are most likely to respond to treatment but
then relapse."
Scientists trying to understand cancer better at a
fundamental level should focus their efforts on cancer
stem cells, he said.
"A lot of research on cancer involves the whole tumor
mass," Dirks said. "If you study the expression of
genes in all those cells you may not be studying the
genes that are the most important."
But perhaps the most important implication is that
identifying and understanding cancer stem cells could
lead to more potent treatments.
"If you think about the basis for leukemia treatment,
generally it is predicated on the idea that leukemia
cells grow faster than the normal cells. So that's
what it goes after," said John E. Dick, a professor of
molecular genetics at the University of Toronto, who
discovered cancer stem cells for acute myelogenous
leukemia.
"But these cells aren't. These leukemia stem cells
are resting. They behave just like a normal stem cell.
They sit there and eventually will regrow the
leukemia," Dick said. "It's critically important to
understand these leukemia stem cells so we can target
them.
"What we need to be able to do is identify these
cancer stem cells to understand their properties so we
can begin to be more strategic and kill the cancer at
its source, which are these cancer stem cells."
That is exactly what Craig T. Jordan, a professor of
medicine at the University of Rochester, has started
to try to do. Jordan has identified a molecular switch
involved in cell survival that appears to be unique to
leukemia stem cells and absent from normal blood stem
cells. "We don't think normal treatments would hit
this target, which is why patients relapse," he said.
Jordan has begun testing drugs that, at least in the
laboratory, appear highly effective at killing
leukemia stem cells while sparing healthy stem cells,
he said.
"It looks fantastic in the lab. In the laboratory we
can very effectively kill the tumor without killing
the normal stem cells," he said.
A preliminary trial involving leukemia patients has
begun at the University of Kentucky, Jordan said.
"It's finally getting to the exciting point," he
said.
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=====
+++++++++++++++++++
"Everyone is ignorant, only on different subjects."
Will Rogers
-- John
John Jacobus, MS
Certified Health Physicist
e-mail: crispy_bird@yahoo.com
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