Because glutaminase catalyzes the conversion of glutamine to glutamate, and the increased activity of this enzyme is at least partially responsible for elevated glutamine metabolism in cancer, including IDH1-mutated tumors [43, 45, 49, 60-64], the fact that BPTES-induced blockade of glutamine flux augmented the sensitivity of IDH1-mutated cells to metformin was consistent with the changes in glutamine metabolism as an adaptive response following metformin treatment. This evidence concerns the gene GLS and cancer.