When medication is used to shut off the oxygen supply to tumors, the cells adapt their metabolism in the medium term -- by switching over to producing energy without oxygen, new research has found.
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Medicines can initially slow or even stop tumor growth. However, as the treatment goes on, the tumors begin to develop resistance to these therapies -- and they start to grow again.
The new findings, reported in the journal Cell Reports, could be used for treatments that can inhibit tumor growth in the long term.
Today, it is common knowledge that the disease develops in a series of stages. One of these stages, tumor angiogenesis, involves the formation of new blood vessels to supply oxygen and nutrients to the growing tumor.
Now, the research team has shown that, although the latest medications are effective at preventing blood vessel formation, the tumors can continue growing even without a supply of new blood vessels.
Analysis of this finding from a biochemical and molecular genetic perspective revealed that the tumor cells convert to a different type of metabolism. They no longer produce energy using oxygen delivered via the blood vessels -- but instead switch over to glycolysis, a form of anaerobic energy production.
The lactic acid formed as a result is delivered to cells that are still receiving sufficient oxygen and that can use the lactic acid, together with the oxygen, to produce energy.
The research group also showed that this specific mode of metabolism -- and therefore the tumor's growth -- can be interrupted, namely by inhibiting anaerobic energy production or transport of the lactic acid.
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"Our findings open up new approaches for the optimization of anti-angiogenic therapies and for inhibiting tumor growth effectively in the long term," said lead researcher Gerhard Christofori, professor at University of Basel in Switzerland.