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Pancreatic cancer

Glutamic-oxaloacetic transaminase 1 (GOT1); malate dehydrogenase 1 (MDH1); NADP-dependent malic enzyme (ME1)

In vitro and mouse studies suggest inhibiting cancer-specific glutamine metabolism could help treat K-Ras-mutant pancreatic cancers. In pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deprivation or small hairpin RNA against GOT1, MDH1 or ME1, which are enzymes involved in cancer-associated glutamine metabolism pathways driven by oncogenic K-Ras, led to decreased cell proliferation compared with no glutamine deprivation or control shRNA. In a mouse xenograft model for human PDAC, shRNA against glutamine pathway enzymes led to decreased tumor growth compared with a control shRNA. Next steps include identifying pharmacological inhibitors of GOT1, MDH1 or ME1 (see Glutamine metabolism drives PDAC, page 4).

SciBX 6(13); doi:10.1038/scibx.2013.310
Published online April 4, 2013

Patent application filed; available for licensing

Son, J. et al. Nat. Med.; published online March 27, 2013;
Contact: Lewis C. Cantley, Weill Cornell Medical College, New York, N.Y.
Contact: Alec C. Kimmelman,
Dana-Farber Cancer Institute, Boston, Mass.