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Keywords | Hypoxia | HIF | pericellular | human | drug |<br />
EUROXY<br />
Targeting newly discovered<br />
oxygen-sensing cascades<br />
for novel cancer treatments<br />
Summary<br />
A fi ve-year eff ort to develop anti-cancer drugs targeting<br />
the hypoxia responsive regulatory pathways in human cells<br />
was fi nished the fi rst two years. It has led to a better understanding<br />
of the therapy resistance of cells at hypoxia and<br />
a much more detailed knowledge about the pathways<br />
involved. To work under controlled conditions, in vitro and<br />
in vivo technology has been developed to keep and record<br />
the peri cellular oxygen tension. It is still unclear if the preferred<br />
target for intervention will be the cells oxygen sensors<br />
upstream from HIF or HIF itself or one of the downstream<br />
molecules like the hypoxia induced electron pumps for<br />
which we are patenting new inhibitors.<br />
Problem<br />
Most solid human tumours have areas where the cells are<br />
exposed to low oxygen tension. Low oxygen tension is correlated<br />
with a bad prognosis. Hypoxic tumour tissues usually<br />
have a lowered susceptibility to conventional treatment with<br />
irradiation and cytostatics.<br />
TREATMENT<br />
Aim<br />
The consortium want to develop a new class of anti-cancer<br />
agents targeting and disrupting the adaptive mechanisms<br />
exploited by human cells when exposed to low oxygen<br />
tensions.<br />
Expected results<br />
Within the remaining three years, the consortium expects to<br />
have a better knowledge of the cellular responses to low<br />
oxygen tension and to know regulatory molecular pathways<br />
important for cell adaptation to hypoxia.<br />
The consortium also expects to have developed a technology<br />
platform for measuring pericellular oxygen tensions<br />
in vitro and in vivo and to have methods for non-invasive<br />
determination of oxygen tensions.<br />
We further expect to have in vitro and animal tested a few<br />
novel and patented compounds for cytostatic eff ects on<br />
human cancer cells kept at in vivo relevant low oxygen<br />
tension.<br />
We ultimately hope to have compounds that will attract<br />
private companies to undertake further development work.<br />
Potential applications<br />
Anticancer drugs.<br />
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