Scientists at Harvard University in the US have discovered tumor cells' ability to alter their metabolism, Report says, citing Cell Metabolism journal.
Cancer relapse begins when malignant cells pass through the extreme metabolic bottleneck of stress from chemotherapy and the byproducts of the massive cell death in the surrounding region.
In acute myeloid leukemia, complete remissions are common, but few are cured. "We tracked leukemia cells in vivo, defined the moment of maximal response following chemotherapy, captured persisting cells, and conducted unbiased metabolomics, revealing a metabolite profile distinct from the pre-chemo growth or post-chemo relapse phase. Persisting cells distinctively used glutamine, preferentially fueling pyrimidine, and glutathione generation, but not the mitochondrial tricarboxylic acid cycle."
Notably, malignant cell pyrimidine synthesis also required aspartate provided by specific bone marrow stromal cells. They are blunting glutamine metabolism or pyrimidine synthesis against residual leukemia-initiating cells and improved survival in leukemia mouse models and patient-derived xenografts. We propose that timed cell-intrinsic or niche-focused metabolic disruption can exploit a transient vulnerability and induce metabolic collapse in cancer cells to overcome chemoresistance.