TROP2 targeting reshapes cell states to overcome therapy resistance in colorectal cancer

The study identifies TROP2 as a marker of poor-prognosis colorectal cancer linked to fetal-like, WNTlow states that drive metastasis and therapy resistance. TROP2+ cells show context-dependent stem-like properties and can seed metastatic outgrowth; chemotherapy expands these populations, while TROP2-directed antibody–drug conjugates selectively target them and remodel the tumor cell-state landscape. Combining chemotherapy with TROP2 targeting enhances anti-tumor efficacy in patient-derived models, revealing a cell-state vulnerability to overcome resistance in advanced CRC.