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Publishing in the journal Nature Metabolism online Nov. 26, study results showed that the low-glucose environment inhabited by cancer cells, or tumor microenvironment, stalls cancer cell consumption of existing uridine nucleotide stores, making the chemotherapies less effective.

The irony, researchers say, is that a low-glucose tumor microenvironment is in turn slowing down cellular consumption of uridine nucleotides and presumably slowing down rates of cell death.

"Our results explain what has until now been unclear about how the altered metabolism of the tumor microenvironment impacts chemotherapy: low glucose slows down the consumption and exhaustion of uridine nucleotides needed to fuel cancer cell growth and hinders resulting apoptosis, or death, in cancer cells," said senior study investigator Richard Possemato, PhD.

Possemato, who is also coleader of the Cancer Cell Biology Program at Perlmutter, says his team's study results could one day be used to develop chemotherapies or combination therapies that would change or trick cancer cells into responding the same way in a low-glucose microenvironment as they would in an otherwise stable glucose microenvironment.

Both T-cells and CAR-T cells can become "exhausted" in the hostile tumor microenvironment.