Only 3 - 5 % of cancer cells in a tumor act cancerous



R

Roger

Guest
At least according to the article below. Seems to
completely change the approach to dealing with cancer since
the cancer stem cells don't have a life cycle like
cancerous non-stem cells.

Roger

------

http://virtualtrials.com/news3.cfm?item=2410

March 11, 2004

Stem Cells in Tumors May Help Explain Some Cancer Mysteries

If anyone still has doubts that the 1950s are a bygone era,
consider some experiments scientists conducted then without
raising eyebrows (let alone lawsuits).

To probe the basics of cancer, a team of scientists injected
cells from patients' colon, lung, ovarian and other tumors
into the patients' own thighs. After trying this with
varying numbers of cells, the scientists found that the
transplants regenerated a tumor in the thigh (or in a mouse)
only if at least one million cells were injected.

If the bioethics of the 1950s fell short of today's, the
science was a harbinger of an upheaval now shaking cancer
biology. After going nowhere for decades, those old results
have finally led to a revolutionary insight.

"Within a tumor mass, there is only a small population of
cells that can spawn more tumor; other cells in the tumor
can't," says cancer biologist Robert Weinberg of the
Whitehead Institute, Cambridge, Mass., who discovered the
first human oncogene.

The existence of these "tumor stem cells" promises to
explain one of the more perplexing, and tragic, mysteries of
cancer treatment. Biologists have made great strides in
identifying molecular pathways by which cancer cells grow
and spread. But although Iressa shrinks non-small-cell lung
cancers, Erbitux shrinks advanced colorectal cancers and the
just-approved Avastin shrinks metastatic colorectal cancer
-- in each case, in only some patients -- the drugs prolong
survival by mere months or not at all.

The reason, says Dr. Weinberg, may be that "killing off the
majority of cells in a tumor will still leave it with the
ability to regenerate another tumor, from these stem cells."

Eradicating the non-stem cells in a tumor "may result in a
remission" and even the appearance of being cancer-free,
explains molecular biologist John **** of the University of
Toronto, but "the disease will relapse if the tumor-
initiating cells are not eliminated."

Discovering that only some cancer cells are able to generate
more tumor has been a struggle, as the lag between those
1950s experiments and today shows.

"The idea of cancer stem cells has been around for a long
time," says biologist Irving Weissman of Stanford
University. But no stem cell (normal or cancerous) had been
isolated until he and his colleagues identified blood-
forming stem cells in mice in 1987, and in humans in 1992.
Seizing on this method for differentiating stem cells from
others, Dr. **** and his team discovered in 1994 that, in
leukemia, only some cells have the ability to spawn more
tumor. The Toronto team dubbed them "leukemic stem cells."

It was an uphill struggle to figure out whether blood
cancers are unique, or whether solid tumors have cancer stem
cells, too. But after begging the university for a crucial
$500,000 machine, biologists led by Michael Clarke and
Muhammad Al-Hajj of the University of Michigan, Ann Arbor,
found last year that breast cancer consists of a few cancer-
initiating cells that can make more breast-cancer cells,
seemingly forever, surrounded by an ocean of noncancer-
initiating cells.

Although the two kinds of cells looked identical, on closer
inspection there were several "markers" -- think of them as
microscopic flags poking up from the cell's surface -- that
distinguish a breast-cancer stem cell from the cells in a
breast tumor that can't generate more tumor. When the
Michigan team injected as few as 100 cells of the former
into mice, breast tumors grew every time. Not even tens of
thousands of noncancer stem cells produced a tumor. Since
the Michigan discovery, researchers in Japan and Canada have
found brain-cancer stem cells; stem cells likely exist in
other solid tumors, too.

Dr. Clarke estimates that breast cancer stem cells make up
as little as 3% to 5% of some tumors. That's the good
news. Those are the only cells you have to kill to cure
cancer, because non-stem cells eventually die off on
their own. Even when non-stem cells spread, they don't
pose much danger because they die after dividing a few
times. The goal of current chemotherapy, to kill as many
cells as possible, can probably be dialed back.

The bad news is that standard chemo hits tumor cells at a
vulnerable point in their life cycle, but cancer stem cells
don't seem to cycle this way. "I think the reason cancer
therapy does not cure all cancers has to do with the unique
properties" of the cancer stem cell, says Dr. ****.

Ever more sobering, the molecular pathways that scientists
have recently identified, with much fanfare, as allowing
cancer cells to grow may not be critical after all. If such
a pathway promotes growth in the zillions of cells that are
not cancer stem cells, it may be inconsequential. The only
pathways that matter are those that keep the miscreants
alive and thriving. Or as Dr. Weinberg told me, "tumor stem
cells may explain why you can have tumor shrinkage but not
life extension. If current chemotherapies don't target tumor
stem cells, the cells keep making more tumor."

On the bright side, knowing which cells they have to kill
gives scientists a better shot at finding therapies that
do that. "I'm optimistic we can figure this out," says
Dr. Clarke.
 
S

Steph

Guest
"Roger" <[email protected]> wrote in message
news:[email protected]...
> At least according to the article below. Seems to
> completely change the approach to dealing with cancer
> since the cancer stem cells don't have a life cycle like
> cancerous non-stem cells.
>
> Roger
>

It's been well established for 30 years that only a small
proportion of the cells in a cancer are able to continually
divide and spread. In many sarcomas, the Cell Loss Factor is
as high as 99% So this is nothing new, and nothing useful
 
R

Roger

Guest
"Steph" <[email protected]> wrote in message
news:[email protected]...
>
> "Roger" <[email protected]> wrote in message news:O3d4c.345-
> 22$aT1.[email protected]
> > At least according to the article below. Seems to
> > completely change the approach to dealing with cancer
> > since the cancer stem cells don't have a life cycle like
> > cancerous non-stem cells.
> >
> > Roger
> >
>
> It's been well established for 30 years that only a small
> proportion of
the
> cells in a cancer are able to continually divide and
> spread. In many sarcomas, the Cell Loss Factor is as high
> as 99% So this is nothing new, and nothing useful

The findings about the existence of the cancer stem cells
appear to be new. The fact that they have a different
life cycle than "harmless" cancer cells appears to be
new. As for the findings being not useful, well maybe not
yet. But I think this is a necessary step to move to the
next step (targeting treatments at the cancer stem cells)
so in the end I think it will be not only useful but a
necessary finding.

Roger
 
S

Steph

Guest
"Roger" <[email protected]> wrote in message
news:[email protected]...
>
> "Steph" <[email protected]> wrote in message
> news:[email protected]...
> >
> > "Roger" <[email protected]> wrote in message news:O3d4c.3-
> > [email protected]
> > > At least according to the article below. Seems to
> > > completely change
the
> > > approach to dealing with cancer since the cancer stem
> > > cells don't have
a
> > > life cycle like cancerous non-stem cells.
> > >
> > > Roger
> > >
> >
> > It's been well established for 30 years that only a
> > small proportion of
> the
> > cells in a cancer are able to continually divide and
> > spread. In many sarcomas, the Cell Loss Factor is as
> > high as 99% So this is nothing new, and nothing useful
>
> The findings about the existence of the cancer stem cells
> appear to be
new.
> The fact that they have a different life cycle than
> "harmless" cancer
cells
> appears to be new. As for the findings being not useful,
> well maybe not yet. But I think this is a necessary step
> to move to the next step (targeting treatments at the
> cancer stem cells) so in the end I think it will be not
> only useful but a necessary finding.
>
> Roger
>

There is no such thing as a "cancer stem cell" There are
cells in a cancer which can't divide, many which can only
divide a few times, then die, and a small proportion of
cells which are "immortal" - I guess this is what you mean.
But that is not new knowledge. The only cells likely to kill
you are the immortal ones, and these are the cells targeted
by radiation and chemo. The only cells responsible for
recurrence are the immortal ones. The only real cancer cells
are the immortal ones..................
 
R

Roger

Guest
"Steph" <[email protected]> wrote in message
news:[email protected]...
>
> "Roger" <[email protected]> wrote in message news:0yd4c.345-
> [email protected]
> >
> > "Steph" <[email protected]> wrote in message
> > news:[email protected]...
> > >
> > > "Roger" <[email protected]> wrote in message news:O3d4c-
> > > [email protected]
> > > > At least according to the article below. Seems to
> > > > completely change
> the
> > > > approach to dealing with cancer since the cancer
> > > > stem cells don't
have
> a
> > > > life cycle like cancerous non-stem cells.
> > > >
> > > > Roger
> > > >
> > >
> > > It's been well established for 30 years that only a
> > > small proportion
of
> > the
> > > cells in a cancer are able to continually divide and
> > > spread. In many sarcomas, the Cell Loss Factor is as
> > > high as 99% So this is nothing new, and nothing useful

What is new is the isolation of these cells. It may have
been known before that there was a subset of such cells but
it's only recently that the stem cell-like cancer cells in a
human breast cancer were isolated from the other cancer
cells and tested on mice. So this is new. It's why it was in
the Proceedings of the National Academy of Sciences in 2003.

And it's a breakthrough because these cells can be examined
closely to see what is unique about them. If they are
somewhat uniform, then it makes the job of finding effective
therapies a lot easier compared to having to deal with a
hundred (or whatever) radically different types of cancer
cells due to mutations.

> >
> > The findings about the existence of the cancer stem
> > cells appear to be
> new.
> > The fact that they have a different life cycle than
> > "harmless" cancer
> cells
> > appears to be new. As for the findings being not useful,
> > well maybe not yet. But I think this is a necessary step
> > to move to the next step (targeting treatments at the
> > cancer stem cells) so in the end I think it will be not
> > only useful but a necessary finding.
> >
> > Roger
> >
>
> There is no such thing as a "cancer stem cell"

According to the researcher (Michael Clarke of the
University of Michigan) who discovered last year the subset
of breast cancer cells in a breast cancer tumor that act
genuinely cancerous, these cells are stem cells in the sense
that all cancer cells come from them. So these cancer stem
cells produce daughter cancer stem cells as well as less
dangerous cancer cells that are not cancer stem cells. Thus
they play a role similar to normal stem cells in that all
cells come from stem cells.

> There are cells in a cancer which can't divide, many which
> can only divide
a
> few times, then die, and a small proportion of cells
> which are
"immortal" -
> I guess this is what you mean. But that is not new
> knowledge.

But what's new is the isolation of them and the testing of
them in mice. The testing consisted of putting 100 of these
cancer stem cells in the mice and a tumor would grow.
Normally 100 cancer cells can not produce a tumor - about
one million are needed. They also tested the non-stem cell
cancer cells and none of them could produce a tumor no
matter how many were injected into the mice.

Thus all the mutations those cancer cells have undergone do
not matter. This is why (if I understand this correctly)
this discovery has the potential to make it a lot easier to
kill a tumor. Now they can zero in on just those cells since
they have them isolated now and see what will prevent them
from making daughter cells and what will kill them.

Roger

The only cells
> likely to kill you are the immortal ones, and these are
> the cells targeted by radiation and chemo. The only cells
> responsible for recurrence are the immortal ones. The only
> real cancer cells are the immortal ones..................
 
M

Madiba

Guest
Steph <[email protected]> wrote:

> "Roger" <[email protected]> wrote in message news:peB4c.361-
> [email protected]
> >
>
> I've been in this game long enough to know you shouldn't
> hold your breath............
. :-/

Speaking of which, you must be blue in the face waiting for
that beer I owe you.. Now if you happen to be in Scotland
again during the last week of March... (3 consultant posts
up for grabs at the Beatson) you could breath easier again
and enjoy a Kilkenny with us. If not, hold thumbs please..
--
Jon
 
S

Steph

Guest
"madiba" <[email protected]> wrote in message
news:1gap9zf.1sxj4nm1gjhgjlN%[email protected]...
> Steph <[email protected]> wrote:
>
> > "Roger" <[email protected]> wrote in message news:peB4c.3-
> > [email protected]
> > >
> >
> > I've been in this game long enough to know you shouldn't
> > hold your breath............
> . :-/
>
> Speaking of which, you must be blue in the face waiting
> for that beer I owe you.. Now if you happen to be in
> Scotland again during the last week of March... (3
> consultant posts up for grabs at the Beatson) you could
> breath easier again and enjoy a Kilkenny with us. If not,
> hold thumbs please..
> --
> Jon

That's 9 consultant posts up for grabs at the Beatson,
Jon...........though they are only advertising 3 at a time.
In fact, I'll let you into a secret...........I was
"invited" to apply for the post of Director but when they
saw my set of proposals for turning the place around, they
decided not to short list me..... Was in the UK in Feb, and
won't be back until next year sometime. Not thinking of a
move to Bonny Scotland yourself, are you?

Don't worry, the pint is in my PalmPilot spreadsheet......
 
M

Madiba

Guest
Steph <[email protected]> wrote:

> "madiba" <[email protected]> wrote in message
> news:1gap9zf.1sxj4nm1gjhgjlN%[email protected]...
> > Steph <[email protected]> wrote:
> >
> > > "Roger" <rog[email protected]> wrote in message news:peB4c-
> > > [email protected]
> > > >
> > >
> > > I've been in this game long enough to know you
> > > shouldn't hold your breath............
> > . :-/
> >
> > Speaking of which, you must be blue in the face waiting
> > for that beer I owe you.. Now if you happen to be in
> > Scotland again during the last week of March... (3
> > consultant posts up for grabs at the Beatson) you could
> > breath easier again and enjoy a Kilkenny with us. If
> > not, hold thumbs please..
>
> That's 9 consultant posts up for grabs at the Beatson,
> Jon...........though they are only advertising 3 at a
> time. In fact, I'll let you into a secret...........I was
> "invited" to apply for the post of Director but when they
> saw my set of proposals for turning the place around, they
> decided not to short list me..... Was in the UK in Feb,
> and won't be back until next year sometime. Not thinking
> of a move to Bonny Scotland yourself, are you?
I was, but if that means carring the workload of the missing
6 perhaps I should reconsider.. Prefer warmer climes
normally so Portsmouth was where I aimed for - but a cute
Finn beat me to the finish.
--
Jon
 
S

Steph

Guest
"madiba" <[email protected]> wrote in message
news:1gar2my.11d896w1h77vasN%[email protected]...
> Steph <[email protected]> wrote:
>
> > "madiba" <[email protected]> wrote in message
> > news:1gap9zf.1sxj4nm1gjhgjlN%[email protected]...
> > > Steph <[email protected]> wrote:
> > >
> > > > "Roger" <[email protected]> wrote in message news:peB-
> > > > [email protected]
> > > > ...
> > > > >
> > > >
> > > > I've been in this game long enough to know you
> > > > shouldn't hold your breath............
> > > . :-/
> > >
> > > Speaking of which, you must be blue in the face
> > > waiting for that beer
I
> > > owe you.. Now if you happen to be in Scotland again
> > > during the last week of March... (3 consultant posts
> > > up for grabs at the Beatson) you could breath easier
> > > again and enjoy a Kilkenny with us. If not, hold
> > > thumbs please..
> >
> > That's 9 consultant posts up for grabs at the Beatson,
Jon...........though
> > they are only advertising 3 at a time. In fact, I'll let
> > you into a secret...........I was "invited" to apply
for
> > the post of Director but when they saw my set of
> > proposals for turning
the
> > place around, they decided not to short list me..... Was
> > in the UK in Feb, and won't be back until next year
> > sometime. Not thinking of a move to Bonny Scotland
> > yourself, are you?
> I was, but if that means carring the workload of the
> missing 6 perhaps I should reconsider.. Prefer warmer
> climes normally so Portsmouth was where I aimed for - but
> a cute Finn beat me to the finish.
> --
> Jon
No shortage of Clinical Oncology jobs in the BMJ. There are
about 60+ unfilled consultant posts in the UK
 
D

Dr Chaos

Guest
On Fri, 12 Mar 2004 16:03:52 GMT, Steph <[email protected]> wrote:
>
> "Roger" <[email protected]> wrote in message news:0yd4c.345-
> [email protected]
>>
>> "Steph" <[email protected]> wrote in message
>> news:[email protected]...
>> >
>> > "Roger" <[email protected]> wrote in message news:O3d4c.-
>> > [email protected]
>> > > At least according to the article below. Seems to
>> > > completely change
> the
>> > > approach to dealing with cancer since the cancer stem
>> > > cells don't have
> a
>> > > life cycle like cancerous non-stem cells.
>> > >
>> > > Roger
>> > >
>> >
>> > It's been well established for 30 years that only a
>> > small proportion of
>> the
>> > cells in a cancer are able to continually divide and
>> > spread. In many sarcomas, the Cell Loss Factor is as
>> > high as 99% So this is nothing new, and nothing useful
>>
>> The findings about the existence of the cancer stem cells
>> appear to be
> new.
>> The fact that they have a different life cycle than
>> "harmless" cancer
> cells
>> appears to be new. As for the findings being not useful,
>> well maybe not yet. But I think this is a necessary step
>> to move to the next step (targeting treatments at the
>> cancer stem cells) so in the end I think it will be not
>> only useful but a necessary finding.
>>
>> Roger
>>
>
> There is no such thing as a "cancer stem cell" There are
> cells in a cancer which can't divide, many which can only
> divide a few times, then die, and a small proportion of
> cells which are "immortal" - I guess this is what you
> mean. But that is not new knowledge. The only cells likely
> to kill you are the immortal ones, and these are the cells
> targeted by radiation and chemo. The only cells
> responsible for recurrence are the immortal ones. The only
> real cancer cells are the immortal ones..................

And do the assays for drug activity differentiate between
the 'immortal' ones and the others?

I would tend to doubt so, and this means that many of the
treatment strategies might be going against the wrong cell
populations.
 
S

Steph

Guest
"Dr Chaos" <[email protected]> wrote in message
news:[email protected]...
> On Fri, 12 Mar 2004 16:03:52 GMT, Steph
> <[email protected]> wrote:
> >
> > "Roger" <[email protected]> wrote in message news:0yd4c.3-
> > [email protected]
> >>
> >> "Steph" <[email protected]> wrote in message
> >> news:[email protected]...
> >> >
> >> > "Roger" <[email protected]> wrote in message news:O3d4-
> >> > [email protected]
> >> > > At least according to the article below. Seems to
> >> > > completely
change
> > the
> >> > > approach to dealing with cancer since the cancer
> >> > > stem cells don't
have
> > a
> >> > > life cycle like cancerous non-stem cells.
> >> > >
> >> > > Roger
> >> > >
> >> >
> >> > It's been well established for 30 years that only a
> >> > small proportion
of
> >> the
> >> > cells in a cancer are able to continually divide and
> >> > spread. In many sarcomas, the Cell Loss Factor is as
> >> > high as 99% So this is nothing new, and nothing
> >> > useful
> >>
> >> The findings about the existence of the cancer stem
> >> cells appear to be
> > new.
> >> The fact that they have a different life cycle than
> >> "harmless" cancer
> > cells
> >> appears to be new. As for the findings being not
> >> useful, well maybe
not
> >> yet. But I think this is a necessary step to move to
> >> the next step (targeting treatments at the cancer stem
> >> cells) so in the end I think
it
> >> will be not only useful but a necessary finding.
> >>
> >> Roger
> >>
> >
> > There is no such thing as a "cancer stem cell" There
> > are cells in a cancer which can't divide, many which
> > can only
divide a
> > few times, then die, and a small proportion of cells
> > which are
"immortal" -
> > I guess this is what you mean. But that is not new
> > knowledge. The only
cells
> > likely to kill you are the immortal ones, and these are
> > the cells
targeted
> > by radiation and chemo. The only cells responsible for
> > recurrence are
the
> > immortal ones. The only real cancer cells are the
> > immortal ones..................
>
> And do the assays for drug activity differentiate between
> the 'immortal' ones and the others?

No. But the immortal ones ( clonogenic cells) for many
cancers can be grown indefinitely in vitro. Ever heard of
HeLa cells? Very commonly used for cancer experimentation,
and all derived from a single cancer patient 20+ years ago.
Still going strong.

>
> I would tend to doubt so, and this means that many of the
> treatment strategies might be going against the wrong cell
> populations.
>

Just because in vitro assays don't work doesn't mean that
the clonogenic cells in a cancer aren't the culprits
 
D

Dr Chaos

Guest
On Wed, 07 Apr 2004 01:57:53 GMT, Steph <[email protected]> wrote:
>
> No. But the immortal ones ( clonogenic cells) for many
> cancers can be grown indefinitely in vitro. Ever heard of
> HeLa cells? Very commonly used for cancer experimentation,
> and all derived from a single cancer patient 20+ years
> ago. Still going strong.

Good. Now what if they have characteristics unlike
spontaneous human cancers? In particular the minority of
human cancer stem cells.

>>
>> I would tend to doubt so, and this means that many of the
>> treatment strategies might be going against the wrong
>> cell populations.
>>
>
> Just because in vitro assays don't work doesn't mean that
> the clonogenic cells in a cancer aren't the culprits

I think we're in agreement.

I think that this new result actually is big news, and ought
to seriously change the nature of cancer research.

Tumor shrinkage means little if it shrinks the wrong 97% of
the cell population.
 
S

Steph

Guest
"Dr Chaos" <[email protected]> wrote in message
news:[email protected]...
> On Wed, 07 Apr 2004 01:57:53 GMT, Steph
> <[email protected]> wrote:
> >
> > No. But the immortal ones ( clonogenic cells) for many
> > cancers can be grown indefinitely in vitro. Ever heard
> > of HeLa cells? Very commonly used for cancer
> > experimentation, and all derived from a single cancer
> > patient 20+ years ago. Still going strong.
>
> Good. Now what if they have characteristics unlike
> spontaneous human cancers? In particular the minority of
> human cancer stem cells.
>

He La is a spontaneous human cancer cell line.........

> >>
> >> I would tend to doubt so, and this means that many of
> >> the treatment strategies might be going against the
> >> wrong cell populations.
> >>
> >
> > Just because in vitro assays don't work doesn't mean
> > that the clonogenic cells in a cancer aren't the
> > culprits
>
> I think we're in agreement.
>
> I think that this new result actually is big news, and
> ought to seriously change the nature of cancer research.
>
> Tumor shrinkage means little if it shrinks the wrong 97%
> of the cell population.

Sensible oncologist have known that (and been saying it) for
years What is more, by the time a cancer is 1cm in size, it
is 3/4 of the way to being 1kg in size............

The "New result" isn't new, and isn't a result. Don't get
too excited
 
D

Dr Chaos

Guest
On Sat, 10 Apr 2004 23:32:34 GMT, Steph <[email protected]> wrote:
>> I think that this new result actually is big news, and
>> ought to seriously change the nature of cancer research.
>>
>> Tumor shrinkage means little if it shrinks the wrong 97%
>> of the cell population.
>
> Sensible oncologist have known that (and been saying it)
> for years What is more, by the time a cancer is 1cm in
> size, it is 3/4 of the way to being 1kg in
> size............
>
> The "New result" isn't new, and isn't a result. Don't get
> too excited

The question is whether the therapies preferentially kill
the 97% of the wrong cells, since they were probably assayed
in drug development by tumor shrinkage.

IF they had a way to assay "%age kill of tumor stem cells"
perhaps the drugs would be far different.
 
S

Steph

Guest
"Dr Chaos" <[email protected]> wrote in message
news:[email protected]...
> On Sat, 10 Apr 2004 23:32:34 GMT, Steph
> <[email protected]> wrote:
> >> I think that this new result actually is big news, and
> >> ought to seriously change the nature of cancer
> >> research.
> >>
> >> Tumor shrinkage means little if it shrinks the wrong
> >> 97% of the cell population.
> >
> > Sensible oncologist have known that (and been saying it)
> > for years What is more, by the time a cancer is 1cm in
> > size, it is 3/4 of the way
to
> > being 1kg in size............
> >
> > The "New result" isn't new, and isn't a result. Don't
> > get too excited
>
> The question is whether the therapies preferentially kill
> the 97% of the wrong cells, since they were probably
> assayed in drug development by tumor shrinkage.
>
> IF they had a way to assay "%age kill of tumor stem cells"
> perhaps the drugs would be far different.

Paradoxically, it is actually the clonogenic cells (your
stem cells) which are the most sensitive to radiation and
chemotherapy.....