1092-Endocytic Evasion & Drug Resistance

Paper Talk · Jun 7, 2026 · 24m

This article from Cancer Cell investigates why some urothelial cancers develop resistance to the antibody-drug conjugate (ADC) Enfortumab vedotin (NECTIN4-ADC). Using single-cell RNA sequencing and spatial transcriptomics, researchers identified a specific tumor cell subpopulation that remains high in NECTIN4 expression but evades treatment through endocytic trafficking defects. The study reveals that the protein AKR1C1 blocks the internalization of the drug and works with WWP2 to export the ADC out of the cell via extracellular vesicles. This resistance state is driven by the transcription…