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TROP2 Pinpoints and Permits Targeted Attack on Metastasis‑Driving Colorectal Cells

Preclinical results show approved TROP2-directed antibody–drug conjugates kill therapy-resistant, stem-like colorectal cells, leading to a Phase 2/3 trial.

Overview

  • Researchers at DKFZ and HI-STEM report in Nature that the cell-surface protein TROP2 marks a subset of colorectal tumor cells linked to worse prognosis and higher metastatic and recurrence risk.
  • Laboratory studies found TROP2-positive cells adopt fetal-like, stem-cell properties that enable them to seed new tumors and resist standard therapies.
  • Clinically approved TROP2-targeting antibody–drug conjugates selectively depleted TROP2-positive cells in patient-derived organoids and prolonged survival in mouse models.
  • Standard chemotherapy was shown to increase the proportion of TROP2-expressing cells in lab models, while sequential or combined chemotherapy plus TROP2 blockade reduced tumor growth and metastasis more than either treatment alone.
  • Clinical translation has begun with a Phase 2/3 trial at Heidelberg testing a TROP2 antibody–drug conjugate in advanced colorectal cancer, but human safety and efficacy results are still pending.