MBR_Issue_28 -February 2017

Malta Business Review
ERC STORY
NOVEL THERAPY STARVES THE ENGINE
DRIVING CANCER CELL GROWTH
European researchers have identified a
novel approach to prevent the growth of
cancer tumours and inhibit them from
spreading, potentially leading to highly
effective treatments with fewer side
effects.
By Peter Frans Martha Carmeliet
The work, conducted in the ECMetabolism
project with support from the European
Research Council (ERC), builds on prior
research into the formation of blood vessels
– a process known as angiogenesis – that
supply tumours with nutrients and oxygen.
Blood vessels also provide a route for cancer
to metastasise from the original tumour and
spread elsewhere in the body.
Current anti-angiogenic therapies aim to
destroy all tumour blood vessels and starve
the cancer cells. But the treatment often
provokes numerous side-effects, while its
effectiveness can be inhibited by patient
resistance and may even increase the risk of
metastasis.
“There was an unmet need for novel antiangiogenic
strategies with fundamentally
distinct mechanisms,” explains Peter
Carmeliet, who led the ECMetabolism
research at the VIB Vesalius Research Center
of KU Leuven in Belgium. So the research team
set out to develop a new anti-angiogenic
concept targeting key metabolic pathways in
endothelial cells which line the blood vessels,
rather than the blood vessels themselves.
“Our work has advanced the current state
of the art and scientific understanding in the
field of metabolism and angiogenesis.”
A LITTLE KNOWN CELL
When the ERC project began more than
five years ago, very little was known about
how endothelial cell metabolism regulates
vessel sprouting, a process in which existing
blood vessels grow offshoots that become
new vessels. Carmeliet hypothesised that
endothelial cell metabolism is the engine
driving vessel sprouting and that turning down
the engine in endothelial cells would provide an
alternative anti-angiogenic treatment. What is
the key to turning down the engine? Glucose,
more commonly known as blood sugar, which
Carmeliet and his team identified as a major
fuel source for endothelial cell metabolism
through a process called glycolysis.
“We showed that endothelial cells are
addicted to glycolysis, and that a partial and
transient reduction of glycolysis by blocking
the glycolytic activator PFKFB3 – using
the commercially available small molecule
compound, 3PO – inhibits pathological
angiogenesis without systemic effects. To
the best of our knowledge, these are the first
findings showing that a metabolic pathway
(glycolysis) can be a target for tumour vessel
normalisation and anti-metastatic therapy,”
Carmeliet says.
Crucially, in vitro and in vivo animal studies
conducted by the ECMetabolism researchers
showed that other cell types do not rely as
much on glycolysis as endothelial cells and
are therefore able to switch to alternative
metabolic pathways, potentially resulting in
far fewer side-effects for patients. Following
on from that ground-breaking research,
Carmeliet and his team are now shifting focus
towards translating the results into metabolic
anti-angiogenic treatment candidates for
new drugs, including screening a library of
existing pharmaceutical compounds for an
alternative PFKFB3 inhibitor that would be
more active and easier to administer.
“The ERC grant gave us the freedom and
trust to pursue innovative, high-risk/highgain
research at the frontline of life sciences,
attracting a critical mass of researchers over
a longer period of time and making significant
progress that would not have been possible
via other funding organisations,” Carmeliet
says. “With this support we have been able
to produce ground-breaking scientific insights
and discoveries in an unexplored research field
that will be of great benefit for the scientific
community and clinical medicine.” MBR
Researcher (PI): Peter Frans Martha Carmeliet
Host institution: Vib, Belgium
Project: Targeting endothelial metabolism: a novel antiangiogenic
therapy, (ECMETABOLISM)
ERC call: Advanced Grant , ERC-2010-AdG, panel LS2
Max ERC funding: 2,365,224 €
Duration: Start date: 2011-05-01, End date: 2016-04-30
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