Article
Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors.
Nature cancer - 1 Jul 2022
Vaziri-Gohar Ali, Cassel Joel, Mohammed Farheen S, Zarei Mehrdad, Hue Jonathan J, Hajihassani Omid, Graor Hallie J, Srikanth Yellamelli V V, Karim Saadia A, Abbas Ata, Prendergast Erin, Chen Vanessa, Katayama Erryk S, Dukleska Katerina, Khokhar Imran, Andren Anthony, Zhang Li, Wu Chunying, Erokwu Bernadette, Flask Chris A, Zarei Mahsa, Wang Rui, Rothermel Luke D, Romani Andrea M P, Bowers Jessica, Getts Robert, Tatsuoka Curtis, Morton Jennifer P, Bederman Ilya, Brunengraber Henri, Lyssiotis Costas A, Salvino Joseph M, Brody Jonathan R, Winter Jordan M
Abstract excerpt
Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis and NADPH...
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