Chelators In Cancer
ironjustice
"Iron-binding drug, Triapine"
Chelators at the Cancer Coalface: Desferrioxamine to Triapine and
Beyond
Yu Yu, Jacky Wong, David B. Lovejoy, Danuta S. Kalinowski and Des R.
Richardson
Iron Metabolism and Chelation Program,
Department of Pathology, University of Sydney,
Sydney, New South Wales, Australia
Requests for reprints:
Des R. Richardson, Iron Metabolism and Chelation Program, Department
of Pathology, University of Sydney, Sydney, NSW 2006, Australia.
Phone: 61-2-9036-6548; Fax: 61-2-9036-6549; E-mail:
d.rich...@med.usyd.edu.au.
Abstract
The importance of iron and copper in cancer biology has been well
established.
Iron plays a fundamental role in cellular proliferation and copper has
been shown to be a significant cofactor for angiogenesis.
Early observations with the chelator used for the treatment of iron
overload, desferrioxamine, showed that it had promise as an anticancer
agent.
These results sparked great interest in the possibility of developing
more effective iron chelators for cancer therapy.
The recent entry into clinical trials of the iron-binding drug,
Triapine, provides evidence of the potential of this antitumor
strategy.
Likewise, chelators originally designed to treat disorders of copper
overload, such as penicillamine, trientine, and tetrathiomolybdate,
have also emerged as potential anticancer drugs, as they are able to
target the key angiogenic cofactor, copper.
In this review, we will discuss the development of these and other
chelators that show potential as anticancer agents.
------------------
Triapine®
http://www.vionpharm.com/products/triapine.html
Triapine® is designed to prevent the replication of tumor cells by
blocking an enzyme necessary for DNA synthesis and repair. Triapine®
is being evaluated in clinical trials sponsored by the National Cancer
Institute.
Q. What is Triapine® and how does it work?
A: Triapine® is a small molecule that inhibits an enzyme,
ribonucleotide reductase, important to the synthesis of DNA. DNA
synthesis is necessary for cancer cells to replicate; therefore
inhibition of the ribonucleotide reductase enzyme can prevent cancer
cells from dividing in the body. Disruption of DNA synthesis in some
cancer cells will also cause their death.
--------------
Control of disease by selective iron depletion: a novel therapeutic
strategy
utilizing iron chelators.
Hershko C.
Baillieres Clin Haematol. 1994 Dec;7(4):965-1000.
Department of Medicine, Shaare Zedek Medical Center, Jerusalem,
Israel.
Recognition of the central role of iron in the generation of toxic,
oxygen-derived species through the Haber-Weiss reaction, the ability
of desferrioxamine (DFX) to prevent the damage associated with free
radical generation in reperfusion injury, and its inhibitory effect
on cell proliferation by inactivation of the iron dependent enzyme
ribonucleotide reductase, resulted in an increasing number of studies
exploring the novel therapeutic applications of iron chelating drugs:
(a) Animal models of reperfusion injury have shown that DFX is able
to
decrease post-anoxic damage to the brain and heart as manifested in
decreased infarct size and improved functional recovery.
Iron chelators may be particularly useful in improving the
preservation
of organs intended for transplantation such as the heart, lung or
kidney.
(b) Anthracycline cardiotoxicity is aggravated by iron and inhibited
by
iron chelators.
Because the mechanism of its antineoplastic effect differs from its
cardiotoxic effect, it is possible to inhibit anthracycline
cardiotoxicity
without interfering with therapeutic efficacy.
In vivo and in vitro animal studies have yielded encouraging results
but
much additional experimental work is still required before iron
chelating
therapy may be advocated for use in patients on anthracycline
therapy.
(c) Cell proliferation can be inhibited by iron chelators through the
reversible inhibition of ribonucleotide reductase, a rate-limiting
enzyme
in DNA synthesis.
This may be exploited for the treatment of malignant disease, and
preliminary studies have already shown that DFX in combination with
multidrug chemotherapy is effective in controlling neuroblastoma and
other
tumours.
However, the contribution of DF to the overall clinical effect is
unclear.
Prospective controlled clinical studies are required in order to
establish
whether the antiproliferative, or cell synchronizing properties of DFX
may
be of practical usefulness in the control of malignant disease.
(d) Control of protozoal infection: Experimental in vivo and in vitro
models
have shown that malarial infection may be inhibited by iron chelating
therapy.
This useful effect of DFX and other iron chelators is most probably
related to
ribonucleotide reductase inhibition.
Clinical studies of asymptomatic P. falciparum malaria and of cerebral
malaria
have shown both an accelerated rate of parasite clearance and earlier
recovery
from coma.
These observations lend new meaning to the term 'nutritional immunity'
and open
new channels for exploring the possibility of controlling infection by
means of
selective intracellular iron deprivation.
Experimental models for studying the effect of iron chelators on
other
intracellular pathogens such as Toxoplasma gondii, Chlamydia psittaci,
or
Mycobacterium tuberculosis should be established.
PMID: 7881162
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Tom
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fer...@paris.com
overload, such as penicillamine, trientine, and tetrathiomolybdate, have
also emerged as potential anticancer drugs, as they are able to target
the key angiogenic cofactor, copper."
There it is in black and white, it is copper. Is copper the cause of
all disease?
ironjustice
snip <<
http://clincancerres.aacrjournals.org/content/12/23/6876.full?ck=nck
"Iron-binding drug, Triapine"
Chelators at the Cancer Coalface: Desferrioxamine to Triapine and
Beyond
Yu Yu, Jacky Wong, David B. Lovejoy, Danuta S. Kalinowski and Des R.
Richardson
Iron Metabolism and Chelation Program,
Department of Pathology, University of Sydney,
Sydney, New South Wales, Australia
Requests for reprints:
Des R. Richardson, Iron Metabolism and Chelation Program, Department
of Pathology, University of Sydney, Sydney, NSW 2006, Australia.
Phone: 61-2-9036-6548; Fax: 61-2-9036-6549; E-mail:
Abstract
The importance of iron and copper in cancer biology has been well
established.
Iron plays a fundamental role in cellular proliferation and copper
has
been shown to be a significant cofactor for angiogenesis.
Early observations with the chelator used for the treatment of iron
overload, desferrioxamine, showed that it had promise as an
anticancer
agent.
These results sparked great interest in the possibility of developing
more effective iron chelators for cancer therapy.
The recent entry into clinical trials of the iron-binding drug,
Triapine, provides evidence of the potential of this antitumor
strategy.
Likewise, chelators originally designed to treat disorders of copper
overload, such as penicillamine, trientine, and tetrathiomolybdate,
have also emerged as potential anticancer drugs, as they are able to
target the key angiogenic cofactor, copper.
fer...@paris.com
"Likewise, chelators originally designed to treat disorders of copper
overload, such as penicillamine, trientine, and tetrathiomolybdate, have
also emerged as potential anticancer drugs, as they are able to target
the key angiogenic cofactor, copper."
There it is in black and white, it is copper. Is copper the cause of
all disease?
ironjustice
snip <<
WHAT .. part .. of .. fkff .. don't you understand .. ?
YOU .. let me repeat .. have .. NOTHING .. to add ..
Giiiiit ..
DOOOOOOO it ..
http://clincancerres.aacrjournals.org/content/12/23/6876.full?ck=nck
"Iron-binding drug, Triapine"
Likewise, chelators originally designed to treat disorders of copper
overload, such as penicillamine, trientine, and tetrathiomolybdate,
have also emerged as potential anticancer drugs, as they are able to
target the key angiogenic cofactor, copper.
Ken
>
> I .. let me repeat .. I have .. NOTHING .. to add ..
Finally the Spamming Canuck Dicksucker admits the Truth
ironjustice
fer...@paris.com
overload, such as penicillamine, trientine, and tetrathiomolybdate,
have also emerged as potential anticancer drugs, as they are able to
target the key angiogenic cofactor, copper."
So it is copper all along which is the cause of all disease?
ironjustice
Robert Miles
<fer...@paris.com> wrote in message
news:4b41ef16$0$11059$1c46...@news.club.cc.cmu.edu...
Unlikely - it's a known part of the natural prion that normally
prevents Alzheimer's disease.
Robert Miles