New path for selectively killing cancer cells discovered — sugar
9 September 2013
Cancer cells can be selectively destroyed by inhibiting their
sugar metabolism when in an induced inactive state, according to
medical researchers in Berlin.
The findings by researchers at Charité Universitätsmedizin Berlin
and the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch,
together with other partners, have been published in the scientific
journal Nature. 
During chemotherapy for cancer treatment, some cancer cells enter
a state known as senescence (programmed growth arrest) in which they
are inactive and no longer divide. Senescent cells, however, produce
protein messenger substances that can cause harmful inflammatory
reactions and pose a risk of cancer recurrence. This state, however,
also creates a weakness that can be targeted to kill the cells.
“We have demonstrated a major increase in energy metabolism in
senescent tumour cells after chemotherapy, and that the cells truly
crave for sugar,” explains Prof Dr Clemens Schmitt, Director of the
Center for Molecular Cancer Research and Executive Supervising
Medical Doctor at the Department of Hematology, Oncology and Tumor
Immunology at the Charité. “Moreover, we could show that these cells
not only produce more energy, but are dependent upon their major
increase in metabolism,” he added.
When the researchers inhibited sugar metabolism in the cells,
they died off. By contrast, short-term inhibition of energy
metabolism has little effect on resting or dividing cells in normal
tissues. The researchers regard the cause for the high energy
consumption in senescent cells as representing another unique
feature: the moment the cells enter the state of senescence, they
produce large quantities of protein messenger substances.
These substances must then be digested, a highly energy-consuming
process, since some of the proteins are toxic. Thus, if either
energy production in the senescent cells or their digestive
processes is blocked, they cannot survive.
“What is unique about this research study is the new
understanding of a potential target structure for treating malignant
diseases: as a rule, current and very promising so called “targeted”
agents specifically inhibit the activity of an altered molecule that
is present in cancer cells,” explains Prof. Schmitt.
Contrary to this, the researchers with their new therapeutic
approach are proposing to use a cancer-specific state, ie cellular
senescence resulting from chemotherapy, as the therapeutic target of
a downstream metabolic therapy to destroy tumour cells, and not just
a single molecule. “This represents a highly promising research
approach at the interface between preclinical research and clinical
trials,” states Schmitt. “The idea behind our approach could be very
relevant in future strategies for treating cancer patients; in view
of this clinical potential, we are currently conducting further
investigations,” he adds.
In addition, the oncologist emphasizes the interdisciplinary
character of the research findings, primarily developed in Berlin,
and says, “This important study has been made possible by the
excellent research landscape in Berlin and the close collaboration
between transnational clinical researchers from the Charité with
primary scientists from the MDC – brought even closer together in
the newly founded “Berlin Institute of Health.”
Dörr JR, et al. Synthetic lethal metabolic
targeting of cellular senescence in cancer therapy. Nature. 2013 Aug
14. doi: 10.1038/nature12437.