Researchers Find a Way to ‘Starve’ Cancer

Source: Vanderbilt University

Summary: For the first time researchers demonstrated that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital nutrient glutamine.

Cancer cells exhibit unique metabolic demands that distinguish them biologically from otherwise healthy cells. The metabolic specificity of cancer cells affords us rich opportunities to parlay chemistry, radiochemistry and molecular imaging to discover new cancer diagnostics and potential therapies. For the first time, researchers from the Vanderbilt University demonstrated that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital nutrient glutamine. This study lays the groundwork for the development of potential “paradigm-shifting” therapies targeting cancer cell metabolism that could be monitored non-invasively by positron-emission tomography (PET) imaging. The research findings were published in the journal Nature Medicine.

ACST2 protein - primary transporter of Glutamine

This computationally derived homology model of glutamine transporter shows small molecule inhibitor binding in the transporter’s orange-red transmembrane region. Credit: Vanderbilt University

Glutamine is an essential amino acid and is involved in many cells functions such as biosynthesis, cell signaling and protection against oxidative damage. As cancer cells divide more rapidly than normal cells they need more glutamine. The primary transporter of glutamine to the cancer cells is a protein called ACST2. Elevated ASCT2 levels have been linked to poor survival in many human cancers. Genetic studies have shown that silencing the ACST2 gene in cancer cells have produced dramatic anti-tumor effects. The research team developed V-9302, the first highly-potent small molecule inhibitor of a glutamine transporter. Targeting glutamine metabolism at the transporter level resulted in reduced cancer cell growth and proliferation, increased oxidative damage and increased cell death. This study represents a potentially viable approach to precision cancer medicine.

Dr. Charles Manning said, “if we could make a PET imaging tracer based on a certain drug that could help us predict which tumors will accumulate the drug and therefore be clinically vulnerable to it? This is the very essence of ‘visualized’ precision cancer medicine.”

More Information: Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models, Nature Medicine (2018).

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