EGFR N-Glycosylation Catalyzed by NDST2 Promotes Lenvatinib Resistance in Hepatocellular Carcinoma.

NDST2-driven N-glycosylation of EGFR at four conserved sites promotes lenvatinib resistance in hepatocellular carcinoma, with NDST2 upregulation correlating with resistance.

• Why it matters: Understanding molecular mechanisms of drug resistance in HCC is crucial for improving treatment outcomes, as current therapies like lenvatinib often fail due to resistance development.
• What they did: Researchers used patient-derived organoids and xenograft models to analyze EGFR glycosylation, identifying NDST2 as the key enzyme mediating site-specific N-glycosylation that enhances EGFR stability and activity.
• The result: Targeting NDST2 through genetic or nanoparticle-based siRNA approaches reversed lenvatinib resistance, suggesting NDST2 as a promising therapeutic target to restore drug sensitivity in resistant HCC.