ARTICLE | Distillery Therapeutics


November 27, 2017 6:44 PM UTC

Mouse studies suggest inhibiting the metabolic enzymes ketohexokinase, NADK or SUCLA2 could help treat KRAS-mutant colorectal cancer. In a xenograft mouse model of KRAS-mutant colorectal cancer, screening of a CRISPR guide RNA (gRNA) library identified ketohexokinase, NADK and SUCLA2 as genes whose knockout decreased tumor burden compared with normal expression. Knockout of the three genes in xenograft mouse models of colorectal cancer also decreased tumor burden more potently in mice with KRAS-mutant tumors than with KRAS wild-type tumors. In the KRAS-mutant model, ketohexokinase or NADK inhibitor tool compounds decreased tumor burden compared with vehicle, whereas in the KRAS wild-type model, the inhibitors had no effect. Next steps could include testing inhibition of ketohexokinase, NADK or SUCLA2 in patient-derived xenograft (PDX) models of KRAS-mutant colorectal cancer...