1363-Cell State Dynamics in Colorectal Cancer

This research identifies TROP2 as a critical biomarker for poor-prognosis colorectal cancer, specifically marking a "fetal-like" cell state linked to metastasis and drug resistance. While traditional chemotherapy often induces these dangerous TROP2+ cell populations, the study demonstrates that antibody-drug conjugates (ADCs) can effectively target and eliminate them. Functional analysis reveals a high degree of cellular plasticity, where tumors shift between LGR5+ stem cells and TROP2+ states to survive therapeutic pressure. By combining standard chemotherapy with TROP2-directed ADCs, the researchers achieved significantly better anti-tumor efficacy in patient-derived models. Ultimately, the findings suggest that successfully treating advanced colorectal cancer requires mechanistically informed therapies that account for these shifting cellular landscapes.

References:

• Vaquero-Siguero N, Georgakopoulos N, Puschhof M C, et al. TROP2 targeting reveals therapy-driven cell state dynamics in colorectal cancer[J]. Nature, 2026: 1-11.