AsianScientist (Aug. 6, 2011) – Scientists at the University of Auckland in New Zealand have designed a new compound that starves certain cancer cells of glucose, depriving them of energy and causing them to die.
The potential of the compound, STF-31, as an anti-cancer drug has been demonstrated by their collaborators from the Stanford University School of Medicine, and the findings have been published in Science Translational Medicine.
The researchers sought to target one of the abnormal features of many cancer cell types: a change in the metabolic processes that turn glucose into energy, known as the Warburg Effect.
“Normal cells can use glucose efficiently, whereas many cancers produce energy inefficiently through aerobic glycolysis. These cells become addicted to glucose and need to import large quantities of glucose to survive,” explains Associate Professor Michael Hay from the Auckland Cancer Society Research Center (ACSRC) and Maurice Wilkins Center for Molecular Biodiscovery.
“Using STF-31 we have shown that it is possible to selectively inhibit the ability of certain cancer cells to take up glucose. This starves them of energy and causes them to die. Importantly, treatment with STF-31 did not appear to cause toxicity in normal cells and so presages a novel way to selectively target cancer cells.”
The research focused on renal cell carcinoma (RCC), the most common form of kidney cancer in adults. Most RCCs possess a specific mutation in the von Hippel-Lindau (VHL) tumor suppressor gene that makes them highly dependent on glucose.
High-throughput screening of more than 60,000 small molecules at Stanford University identified a simple compound capable of selectively killing VHL-mutant RCC cells.
Based on this lead, medicinal chemists at the ACSRC created a series of drugs, including STF-31, for testing in the laboratory and showed that they acted by inhibiting a protein that transports glucose into cells.
It was shown that STF-31 reduced glucose uptake by RCC tumors in mice, and significantly slowed tumor growth.
As RCC is only one of many cancer types that become dependent on increased glucose uptake, STF-31 has the potential to be an effective against a broad range of cancers.
STF-31 has been licensed for preclinical testing to Ruga Inc., a biotechnology company based in the United States.
The article can be found at: Chan DA et al. (2011) Targeting GLUT1 And The Warburg Effect in Renal Cell Carcinoma By Chemical Synthetic Lethality.
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Source:The University of Auckland.
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