Dear FRiends,
Sorry for the way this message is being transmitted. But i have
abstracted from the NCI files for your review and support of further
information about the new hopeful drugs. Thanks to Giles Friedman for
the website. I will keep you all posted as I learn more, when I call the
N.C.I. again on mOnday and try to find out where the trials may be
conducted.
Cindy asked a question whether the drugs will be utilized for all
cancers. I looked over the web site and learned there are many messages
and comments about the drugs from many specific organizations, like
Prostate, Ovarian, Breast, etc...and many more.
God Bless
marty auslander
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Hi all,
looks like the article is easier to read this way.
Ina
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on cancer"
[The Philadelphia Inquirer] Page One
Sunday, March 16, 1997
A theory on cancer provokes new hope
Tumors need capillaries. Why not try to stop them from
growing?
By Faye Flam
INQUIRER STAFF WRITER
BOSTON -- Thirty-five years ago, while trying to develop
a new blood
substitute for the Navy, Judah Folkman thought he might
have stumbled on a
way to cure cancer.
He met with years of ridicule and scorn from the
scientific community. Now,
though, he has finally won acceptance for his idea,
which has spawned nearly
a dozen new drugs that are being tested on cancer
patients around the
country.
The drugs work by stopping a function that appears to be
vital for tumors --
the growth of hair-thin blood vessels called
capillaries. These new
medicines offer a line of attack that promises to spare
patients the toxic
side effects of chemotherapy.
``With chemotherapy, the idea is to poison every cell in
the body and hope
the poison works more on the tumor cells than the
healthy ones,'' says James
Pluda, a senior drug investigator at the National Cancer
Institute in
Maryland. ``This is a novel approach . . . what you are
doing is effectively
starving the tumor cells.''
Last month, Folkman, 64, a surgeon at Children's
Hospital in Boston and a
professor at Harvard Medical School, along with
colleague Michael O'Reilly,
announced a new drug called endostatin.
Judging from tests in mice, he says, ``it looks like the
best anti-cancer
drug we have'' among this new family of drugs, says
Folkman.
It could take a decade or more of clinical testing
before this drug becomes
available, however, and only people with advanced
cancers that haven't
responded to any other treatments will be able to get
into the drug trials.
Not only that, but the very first human tests will use
doses so small that
they are unlikely to be of help.
Folkman's discovery came in the early 1960s when, as a
doctor drafted by the
Navy, he was asked to find a substitute for blood. At
that time, there was
no way of keeping fresh blood supplies aboard ships.
Folkman says he was testing a substitute based on just
one component of
blood, hemoglobin, running various experiments to
compare it with whole
blood.
The basic test, he said, was to see if the hemoglobin
could keep organs
alive -- for instance, thyroid glands taken from
rabbits.
A thorough scientist, Folkman went so far as to test the
hemoglobin solution
on thyroid glands that had been implanted with melanoma
tumors. If whole
blood kept such tumors alive, would hemoglobin alone?
To his surprise, he found that the tumors didn't die,
but they didn't grow
in the expected way, either. They reached the size of
small peas, then
stopped.
It was then that Folkman was struck by an idea that
would preoccupy him for
three decades.
Malignant tumors need a constant blood supply to grow.
In order to siphon
this blood from healthy tissue, they sprout thousands of
new capillaries.
Perhaps, he reasoned, stopping angiogenesis -- this
capillary-growing
process -- was the way to fight cancer.
In principle, such an attack could zero in on tumors
without harming the
rest of the body. The only places where new capillaries
normally form are in
wounds that are healing and in the female reproductive
system, during the
monthly buildup of the uterine lining.
New blood vessels also grow like tiny vines through the
eyes of people
suffering from diabetes and from a blinding disorder
called macular
degeneration.
Stopping angiogenesis would cause women to miss their
periods, but this
temporary infertility would be an insignificant side
effect compared with
the hair loss, wasting and nausea that come with
standard cancer treatments.
Still, Folkman's vision was met with skepticism. Funding
agencies turned
down his requests for money, students shunned his
laboratory, and he was
rarely invited to give lectures.
``Even people at our own school [ Harvard ] thought we
were nuts,'' he said.
Over time, Folkman began to doubt his own idea. ``At
each point you don't
know if you'll make it to the next point,'' he said of
his own work.
``There's no road map there.''
Even when scientists finally acknowledged that
angiogenesis was essential
for tumor growth, they doubted that Folkman could figure
out a way to halt
it.
But with persistence, Folkman managed to eke out enough
money to keep going
and to attract a few young researchers to his quest.
Again, it was an accident that led to the first
potential drugs. In 1985,
Donald Ingber, a young researcher working in Folkman's
lab, found that a
sample of blood vessel cells, called endothelial cells,
had somehow become
contaminated by a fungus.
``Normally you are supposed to throw away any culture
that gets infected
with a fungus,'' says Folkman. But Ingber refused to
throw it out after
noticing that the fungus seemed to stop the growth of
the blood vessel cells
he was growing in his dish.
That fungus turned into Interferon alpha, which is now
being tested on
terminal cancer patients for whom nothing else has
worked.
Three years ago, another researcher, Robert D'Amato,
realized that since
angiogenesis was necessary for women's menstrual cycles,
one way to find
angiogenesis inhibitors might be to look for drugs that
halted menstruation.
D'Amato, with a background in ophthalmology, was not
interested in cancer
but in macular degeneration, the eye disease.
One substance known to stop menstruation is thalidomide,
made infamous when
women in Europe took it for morning sickness and
subsequently gave birth to
thousands of babies with deformed arms and legs. D'Amato
realized that
thalidomide had prevented the formation of blood vessels
in the developing
fetuses.
Thalidomide, which is now used for leprosy, may further
redeem itself for
fighting cancer and macular degeneration. The drug is
being used for the eye
disorder in a clinical trial at the University of
Pennsylvania Medical
Center.
Researchers are careful to make sure the drug causes no
more birth defects.
Most patients in the macular degeneration trial are too
old to worry about
this, says Penn ophthalmology professor Allen Ho. ``The
patients do get a
kick out of it when we ask them if they could be
pregnant and they're 70.''
Already, thalidomide has been shown to fight cancer in
animals and is poised
to be tried in humans.
This growing field of research is starting to connect
with the study of
tumor suppressor genes, especially one called p53,
which, when damaged or
defective, allows tumors to grow.
Noel Bouck, who studies p53 at Northwestern University,
said she had an
epiphany two years ago at one of Folkman's lectures.
``It was the closest
thing to a revival meeting I've ever seen in science,''
she said. ``I wanted
to get up and say, `I believe!' ''
Bouck was studying how this gene, when healthy, might
prevent cancer. ``When
Folkman mentioned angiogenesis, a light went off,'' she
says.
Eventually she found that healthy p53 does regulate the
manufacture of a
natural angiogenesis inhibitor called thrombospondin --
another potential
new drug.
[ * ]
The newest angiogenesis inhibitor to come from Folkman's
laboratory,
endostatin, is extracted from tumors themselves.
``It's very counterintuitive,'' says Folkman of the idea
that a tumor would
supply a tumor-killing substance. However, it is common
experience for
surgeons, he says, to remove a major tumor, only to
later see it replaced by
an explosion of smaller ones.
Perhaps, says Folkman, the big tumor sends out some sort
of chemical
messenger that cuts off the blood supply to microscopic
tumors -- as if they
were competing with one another for the same resources
in the body. But once
the big one is gone, the small ones thrive.
After testing hundreds of tumor-produced substances,
Folkman's colleague
O'Reilly found endostatin, which, in mice at least, not
only halted but
actually destroyed tumors.
Though endostatin has yet to be tested on people, other
drugs of its type
are passing preliminary tests.
At the Scripps Research Institute in La Jolla, Calif.,
David Cheresh is
leading a clinical trial of vitaxin -- an antibody that
blocks one of the
substances necessary for tumors to promote new blood
vessels.
At British Biotech, based in Annapolis, Henrik Rasmussen
is testing a drug
called marimastat that was originally studied for
arthritis.
It could take a decade for these drugs to reach the
market. But to Folkman's
chagrin, one product -- shark cartilage -- is already
being sold with the
claim that it chokes off cancers.
It was the discovery of angiostatin in the late 1980s
that started the fad,
he says. The problem with shark cartilage, Folkman says,
is that it contains
only traces of angiogenisis inhibitors. And these don't
survive the
digestive system.
``There's no way it would get into the bloodstream and
destroy tumors,'' he
says.
The other problem is quantity: ``You'd have to eat a
whole shark or two
every day.''
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