@article {1628711,
	title = {Induction of a Timed Metabolic Collapse to Overcome Cancer Chemoresistance},
	journal = {Cell Metab},
	volume = {32},
	number = {3},
	year = {2020},
	month = {2020 09 01},
	pages = {391-403.e6},
	abstract = {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 used glutamine in a distinctive manner, 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. Blunting glutamine metabolism or pyrimidine synthesis selected 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.},
	keywords = {Animals, Antineoplastic Agents, Drug Resistance, Neoplasm, Leukemia, Myeloid, Acute, Mice, Mice, Congenic, Mice, Inbred C57BL, Mice, Inbred NOD},
	issn = {1932-7420},
	doi = {10.1016/j.cmet.2020.07.009},
	author = {van Gastel, Nick and Spinelli, Jessica B and Sharda, Azeem and Schajnovitz, Amir and Baryawno, Ninib and Rhee, Catherine and Oki, Toshihiko and Grace, Eliane and Soled, Heather J and Milosevic, Jelena and Sykes, David B and Hsu, Peggy P and Vander Heiden, Matthew G and Vidoudez, Charles and Sunia A Trauger and Haigis, Marcia C and Scadden, David T}
}
