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Monday 29 August
Smart bomb for cancer therapy
A new system for directing radiation
to target cells has been developed in Melbourne. The new targeting system has
the potential to specifically destroy cancer cells with minimal damage to
healthy tissues.
The new targeting concept, for which
an international patent is pending, uses a special class of radioactive atoms
for which the radiation damage is confined to the molecules immediately adjacent
to the radioactive atom.
The cell-killing effect is maximised
by directing the radiation to the genetic material (DNA) of the target cell,
with little effect on neighbouring cells.
“We expect that our targeting system
will be particularly useful for small clusters of cancer cells, such as those
that spread throughout the body when a cancer becomes more advanced,” says Dr
Tom Karagiannis, research officer with the Peter MacCallum Cancer Centre where
the system was devised.
Conventional cancer therapies such
as surgery, radiotherapy and chemotherapy have resulted in a steady decline in
cancer mortality rates over the years. Only chemotherapy has the potential to
be effective when the cancer has spread throughout the body, but often it is not
effective.
Latest figures from the World Health
Organization show that about 50 percent of cancer patients still die in
developed countries and about 80 percent die in developing countries.
A unique feature of the cancer
targeting system is the highly focussed damage caused by the radioactive
isotopes used - most of the radiation damage is within a distance of only a few
millionths of a millimetre. This means they can kill cancer cells without
causing significant damage to normal cells.
The new technology combines
knowledge from a wide range of scientific disciplines, including radiation
biology, chemistry and immunology, Dr Karagiannis says. The key ingredient is a
complex composite drug, made by attaching the radioactive atom to a DNA-binding
molecule, which in turn is linked to a cancer-targeting protein such as an
antibody.
“Our radiolabelled DNA-binding drug
alone provided a very efficient ‘molecular bomb’ for destroying cells,” says Dr
Karagiannis. “But it could not discriminate between cancer cells and healthy
cells.”
To make a ‘smarter’ drug,
researchers took advantage of the fact that many cancer cells express high
levels of certain proteins on their cell surface. Antibodies that bind
specifically to these surface proteins were used as vehicles to target the
lethal damage to cancer cells.
“Our strategy builds on the growing
interest in antibodies as cancer therapeutics,” says Associate Professor Roger
Martin, Tom’s supervisor who has been working on the project concept for the
past three decades.
“There are a currently only a
handful of such anticancer-antibodies that have been approved for therapy and
many others that are in clinical trials.”
Proof-of-principle studies with the
new targeting system have yielded very promising results with cell cultures, but
a commercial partner is required for further development.
Tom is one of 13 Fresh Scientists
who are presenting their research to the public for the first time thanks to
Fresh Science, a national program sponsored by the Federal and Victorian
Governments. One of the Fresh Scientists will win a trip to the UK courtesy of
the British Council to present his or her work to the Royal Institution.
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| Tom
standing next to a DNA model showing the 'smart bomb' in pink and
yellow. The pink is the drug which binds to the DNA. It is attached to a
radioactive atom, seen in yellow, which is brought up close to it's
target - the DNA of the cancer cell. |
Tom
examines the effect of his smart bombs on the survival of cancer cells. |
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Researchers can monitor the
uptake of the DNA binding drug by staining the drug
bright blue.
This image is of human
leukemia cells with the DNA binding drug showing up in the nuclei. They
are visualised under a ultraviolet light.
Photomicrograph by Dr Tom Karagiannis
Research Officer, Molecular Radiation Biology Peter MacCallum Cancer
Centre |
This
is a model of DNA (grey) showing the
designed drugs
(blue/green) binding
tightly in the minor groove. The
drugs are
attached to
radioactive atoms (pink).
Model prepared by Associate Prof. Roger
Martin Head, Molecular Radiation Biology Peter MacCallum Cancer Centre
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Peter
MacCallum Cancer Centre
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