In recent years, interest in the Warburg effect (abnormal metabolism of cancer cells) has re-emerged. The rationale for this treatment strategy is to starve tumor cells while allowing healthy cells to survive alone.
Researchers at the University of Emery's Winship Cancer Institute have identified a transport enzyme called ASCT2 as a target for anticancer drugs, which is responsible for bringing amino acids into cells. Deletion of the gene encoding this enzyme prolongs the survival of invasive leukemia (AML/acute myeloid leukemia) mice - from 45 days to more than 300 days.
ASCT2 can transport some amino acids, such as glutamate. In leukemia cells, the absence of ASCT2 has an overall effect on cellular metabolism, interferes with leucine influx and mTOR signaling, and induces apoptosis.
The study found that in mice, the gene encoding ASCT2 can be deleted without substantial disruption of blood cell development. However, under the pressure of chemotherapy or radiotherapy, the ability of this mouse to restore white blood cell count is indeed slower.
"So far, research on finding therapeutic targets in amino acid metabolic pathways has been slow. These targets must kill cancer cells, but retain normal cells. ASCT2 is dispensable for normal blood cell development, but it is important for the development and processes of leukemia." the researchers said. “Although research strongly recommends ASCT2 as a target for leukemia treatment, clinical trial researchers need to carefully combine ASCT2 inhibitors with chemotherapy.”
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