Nat Med weighs a lot! Target amino acid metabolism precisely, so that cancer cells can't starve

Researchers from the University of van der Waals Medical Center (VUmc) have shown for the first time that a small molecule inhibitor that inhibits glutamine uptake can starve tumor cells and prevent their growth Their breakthrough findings were recently published on Nature Medicine, laying the foundation for the development of subversive therapies targeting cancer cell metabolism "Cancer cells exhibit unique metabolic characteristics that allow us to distinguish them biologically," said study co-author Dr Charles manning of the vandewald molecular probe center "The unique metabolic characteristics of tumor cells give us many opportunities to develop new diagnostic and therapeutic methods using chemistry, radiochemistry and molecular imaging." Glutamine is an essential amino acid for many functions of cells, including biosynthesis, cell signaling and protection from oxidative stress Because cancer cells divide faster than normal cells, they need more glutamine An opal called acst2 is the main transporter of glutamine into cancer cells The high level of acst2 is related to the poor prognosis of many cancers However, the silencing of acst2 can produce significant antitumor effect VUmc's team went one step further: they developed the first powerful small molecule inhibitor for glutamine transporters: v-9302 Inhibition of acst2 expression by v-9302 in tumor cells in vitro and in mouse models can significantly slow down the growth and proliferation of cancer cells, increase oxidative stress damage and cancer cell death "Targeting glutamine metabolism at the transporter level is a potentially accurate cancer treatment." The author concludes However, "in order to target glutamine dependent patients, this new inhibitor requires reliable biomarkers," they said This is because the tumor response to v-9302 is more dependent on the activity of acst2 than the expression of the gene Fortunately, a new pet probe can be developed to detect tumor cells by detecting the glutamine metabolism rate of tumor cells and normal cells VUmc is conducting five clinical trials to determine whether the new pet probe, called 18f-fspg, can detect tumors in the lung, liver, ovary and rectum Manning and colleagues are also pushing other PET probes, such as 11C glutamine, to the clinic to detect glutamine metabolism By attaching radionuclides to v-9302, Manning's team was also able to observe whether the compounds reached the target site of glutamine metabolized tumor site "It has to be exciting," Manning said "If we can develop pet contrast agents based on a specific drug, it will help us predict which tumors can enrich the drug and whether they have clinical value This is very important for visual and accurate tumor treatment " Gram cancer center is currently funding Manning's development of a so-called therapeutic diagnostics tool - a combination of therapeutics and diagnostics.