Cancer-A stop sign
for cancer
A
Stop Sign for Cancer
Dec. 13, 2013 — A
particularly aggressive form of leukemia is the acute lymphoblastic leukemia
(ALL). It is especially common among children and very difficult to treat. Researchers from the
University of Veterinary Medicine, Vienna have now discovered completely new targets for the
treatment of blood cancers. Studying the cancer protein STAT5, the
scientists found new opportunities for the development of effective anti-cancer
drugs. The research team published the scientific work, which could also become
relevant for other types of cancer, in the Journal Leukemia.
Proteins in cells
communicate like relay runners in a competition. The sticks that are
transferred between the runners are the "signals." These signals are
passed within the cell from one protein to another and ensure cell growth and
survival. In cancer cells it is interesting approach to block this information
cascade and thereby block the proliferation of cancer cells.
Essential for the signalling in
cancer cells is the protein STAT5. It is known that STAT5 is overstimulated in many
cancers. It forwards signals in an uncontrolled manner and is ultimately
responsible for the excessive cell division of cancer cells. In mice that
suffer from leukemia, it has already been shown, that the elimination of STAT5 makes the animals gain
health again. Therefore, the importance of the protein in cancer is
obvious. The researchers now want to apply this information on cancer therapy
in humans.
Slowing down STAT5
The research team led
by Veronika Sexl from the Institute of Pharmacology and Toxicology at the
Vetmeduni Vienna took a closer look at STAT5. Using leukemia as a model
disease, the team looked for therapeutically exploitable attack points on the
protein and they actually identified such. The shutdown of two distinct signals
of STAT5 led to a significantly later progression of leukemia in mice compared
to animals that harbored the unmodified STAT5. One of these two therapeutically
relevant sites is of particular importance: "The shutdown of the site Serin779 on STAT5 makes
it impossible for STAT5 to fulfil its role as a relay runner and migrate into
the nucleus. Thus, the effect of STAT5 is inhibited," says Hölbl-Kovacic,
one of the lead authors of the pioneering publication.
Interrupting the
relay race at several points
In a large-scale
screening, the co-lead author Angelika Berger identified those relay runners
that act before Serin779, the so-called PAK (p21 activated kinase). This means that PAK has control over STAT5 and
activates it. By
inhibiting PAK, STAT5 is turned off and disconnected from the relay race.
The cancer researchers also found that PAK is still active, when cancer cells
have already been treated with the current standard therapeutic agent Imatinib. This means that a
potential new drug that acts on PAK could be well used in combination with
Imatinib. Such a strategy would be of great importance in patients that no longer respond to Imatinib
and are "therapy-resistant." PAK kinases thus represent a new
therapeutic target, which is independent of previous treatment methods.
STAT5 has a role in
many cancers
Angelika Berger
explains: "So far, the PAK kinases have received relatively little
attention in cancer therapy. However, they could be beneficial for a wide range
of applications. All types of cancers, in which STAT5 plays a role, could be
treated by this system in a new way. Those are the leukemias but also a number
of other diseases such as breast cancer or prostate cancer."
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