Release date: 2018-01-22
Earlier, Exploring Jun reported that a cheap cold medicine was confirmed to be "starved" to cancer cells. Now, the journal Nature Medicine provides a "coup" to destroy cancer cells by blocking nutrition: scientists have for the first time discovered a novel compound that blocks tumor metabolic pathways and inhibits tumor growth.
“Different from normal healthy cells, tumor cells require special metabolic needs,†says Charles Manning, research team leader and article author. “These additional requirements give scientists the opportunity to discover potential through chemistry, radiology, molecular imaging, and more. Cancer treatment."
He led the team to find a new type of small molecule compound that blocks cancer cells from absorbing the essential nutrient, Glutamine, to inhibit tumor growth.
Image source: Journal (doi:10.1038/nm.4464)
New tricks can "starve" cancer cells
Glutamine is an essential amino acid for many cells to maintain normal function, including biosynthesis, cellular signaling, and prevention of antioxidant damage. Cancer cells divide much faster than normal cells, so they need more glutamine.
Studies have shown that ACST2 protein is the main transporter of glutamine into cancer cells. In cancers such as lung cancer, breast cancer, and colon cancer, up-regulation of ACST2 protein levels is associated with patient survival. When the ACST2 gene expression is inhibited, the growth of cancer cells is significantly inhibited.
The Charles Manning team believes that targeting glutamine metabolism is a "potential strategy to accurately fight cancer." Based on this speculation, they developed the first small molecule inhibitor, V-9302, which strongly targets ACST2 protein, and confirmed that V-9302 can block the expression of ACST2 protein, resulting in decreased cancer cell proliferation and oxidative damage. Increase, eventually leading to death.
However, they stressed: “When using this new inhibitor to treat glutamine-dependent tumors, the corresponding biomarkers need to be validated.†This is because the response of V-9302 depends largely on ACST2 transport. The activity of the body, not the expression of the ACST2 protein.
Shown is a model of V-9302 targeting a glutamine transporter (Source: Vanderbilt University)
"Visualization" precision anti-cancer
More importantly, they combined non-invasive positron emission tomography (PET) with this small molecule inhibitor – by attaching an imaging isotope to V-9302 drugs. Whether V-9302 can target real-time monitoring of glutamine rapidly metabolizing tumors.
Currently, the research team at the Vanderbilt University Medical Center is conducting five clinical trials to test the potential of a new PET tracer called 18F-FSPG for the diagnosis of lung cancer, liver cancer, and ovarian cancer.
Charles Manning said: "If we can achieve tumor visualization monitoring with a specific drug, it will advance the precise treatment of cancer."
Source: Bio-Exploration
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