Targeting cancer cell glycosphingolipid synthesis for antitumor immunity in KRAS-mutant cancers

Inhibiting de novo synthesis of glycosphingolipids, a component of cellular membranes that regulates cell signaling, in cancer cells could help treat KRAS-mutant cancers by increasing tumor IFNγ receptor expression and signaling, which arrests tumor proliferation and promotes inflammatory activity.

CRISPR/Cas9 loss-of-function screening in KRAS-mutant syngeneic mouse models of pancreatic and lung cancer, with and without an intact immune system, identified de novo glycosphingolipid synthesis as required for tumor growth in immunocompetent mice, but not in immunodeficient mice...